My favorite is the Dimesional Cannon from the Tenchi Muyo Movie. It isn’t that big, but it makes the Death Star’s main gun seem like a pea shooter. The Dimesional Cannon is normally used to take out small galaxies.
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From the game Tales of the Floating Vagabond, The Cute Death Grenade. You throw it at an opponent and it opens a portal to the dimension of carnivorous teddy bears which swarm out and attack them. Its a classic.
Ah yes, Tales From the Floating Vagabond. The game that gave us the DPTMP weapon class (“don’t point that at my planet”).
From Babylon 5:
-PPGs.
-Beam cannons, the ones found on capital warships.
From Star Wars:
-Lightsabers.
-Blasters, preferably the rifles.
-Ion cannon (the one on Hoth that swatted Imperial Star Destroyers out of orbit like gnats).
-DEMP guns from the roleplaying game. Essentially a man-portable ion cannon for use against droids. Worked even better against artificial intelligence than Jim Kirk’s voice.
-The quad-guns on the Millennium Falcon.
-The Incom T65C-A2 X-Wing. Damn if the whole thing doesn’t look like a weapon.
-The Incom/Subpro Z-95 Headhunter, first mentioned in one of the Han Solo novels. Later versions of the fighter turned up in the roleplay game all the time, and it was “historically” the basis of the X-Wing design.
From Ringworld:
-The TASP. Unworkable idea, but cute.
From the Hitchhiker’s Guide series:
-The Total Perspective Vortex. Not exactly a weapon, but a great concept.
-Anything named “Kill-O-Zap” or “MegaHurts.”
From Star Trek:
-Jim Kirk’s voice, when used against computers.
-Photon torpedoes, but only from the movies. Beautiful special effect in ST:TMP and ST:WoK.
-Klingon fighting knives. Would make Crocodile Dundee run screaming like a bitch.
That’s all for now.
It’s called a reflex cannon. Definitely gets my vote too- remember, they once destroyed an entire space fleet with that thing.
Nah.
The Death Star was nice and all, but I have to agree that a Star Destroyer–or better yet, a Super Star Destroyer–would be a really cool thing to tool around the galaxy in. A Super Star Destroyer with five or six Star Destroyers for escort duty, natch. And TIE fighters–lots of TIE fighters. (Even though I know it makes no sense whatsover, scientifically speaking, I love the sound TIE fighters make when the scream by.)
Okay, okay, you got me, no alpha rays. It was off the top of my head. Still, the Star Wars universe has a few nice toys.
From the Jedi Academy novels, which really sucked, there’s the Sun Crusher.
Size of a freighter, plus or minus, completely invunerable, shoots a torpedo that destabilizes suns, makes them go nova.
From Darksaber, the Darksaber, a poorly constructed and nonfunctional Death Star, with all the useless bits removed.
From Dark Empire, the Galaxy Gun. Fires huge missiles through Hyperspace.
From Dark Empire, the World Devestators. See, they eat your planet, and turn it into robots to kill you with. Economical!
From… I can’t recall, the Eclipse, I think. Super Star Destroyer with a Death Star cannon built in it.
The SDF’s main gun was the Reflex Cannon, yep.
From Trigun: Vash the Stampede’s Angel Arms.
From: I can’t remember… The nanobullet. Shoot someone, turn them into goo.
From OGRE, by Steve Jackson Games:
The OGRE. Sort of like a Bolo.
From: Paranoia. Well.
Anything.
The second best weapon was old Markie, the equivalent of a Bolo or OGRE… with severe personality issues.
The best weapon, of course, was the Computer.
Note that the Sinclair Molecule Chain appeared there, before Gibson used it, as well. You open the magnetic container it was in, it fell to the center of the earth. Hey, what was there to hold it?
Nobody’s mentioned Reason, from Snow Crash, yet?
My favorite weapons, of course, are all the ones I’ve made up myself…
But aside from THOSE…
StarCraft:
Siege Tanks- Not as powerful as some of these others, but it creates a really satisfying PHOOM!!! when fired.
Star Wars:
Concussion Rifles- Seen only in the computer games. Very powerful hand-held weapon that makes a BWAH!!! sound when fired.
Aliens:
Autorifles- Not only do they sound cool as hell, look cool as hell, but they’ll track the enemy for you.
Star Trek- The Hirojin(sp?) hunting rifles. Big, bad, and ready to kick some ass.
Others:
The laser from Congo- Yeah, the movie sucked, but when the chick finally got the laser up and running, it sliced through those mutant monkeys like a hot knife through butter.
Black Shark missiles from Descent3: You shoot 'em, they detonate, and create a miniature black hole to suck all surrounding matter into. Note: Make sure you’re well away from the blast area when it goes off.
The BFG from Doom/Quake: Big Fuckin’ Gun. The name says it all.
The Railguns from Eraser: There’s the enemy, fifteen miles away! ::bang:: And now he’s dead! Plus, the ultra-nifty air-distortion effect is a big plus.
From SW:
Boba Fett. The guy was a walking weapon. I’d kill for a fully operational suit of Mandalorian Armor.
Lightsabers. 'Nuff said.
TIE Interceptors. All the sound and menacing look of a TIE Fighter, all the guns of an X-Wing.
Turbolaser Batteries. The name just sounds cool.
And of course, the biggest, baddest ships in the galaxy, the mighty Imperial Star Destroyer. While a Super Star Destroyer maybe be even bigger and can blow more stuff up, you just can’t beat an Imperial Star Destroyer (They could take the Enterprise-E any day of the week, IMO).
From ST:
Chronaton (sp?) Torpedoes, from the Year of Hell episode of Voyager. They just kick ass!
Klingon Birds of Prey. They just look cool.
From Starcraft:
Protoss Psi Blades, Psi Storm and Psionic Shockwave. Anything with Psi preceeding it has to be cool, right?
(BTW, don’t comment on my ISD vs. Enterprise remark…I know how the debate can get riled up and I dont wanna hijack the thread, I just thought it needed to be said)
The Soft Weapon, from Niven’s “The Soft Weapon”.
‘Reason’, from Neal Stephensons ‘Snow Crash’.
Man, I can’t believe no one’s mentioned E.E. “Doc” Smith’s books. He was the master of cool weaponry. I mean, OK, it was really cheesy space opera, which helps, but still!
My personal favorite was the idea of hooking up inertialess drives to entire planets, which the opposing sides would then fling at each other. By a few books into the series, each side would have a few dozen planets flying along with their fleets, ready to hurl at the enemy. Damn. That rocked. See, when you shut off the inertialess drive, the planets’ “intrinsic” inertia would return - it would go back to the exact speed and direction it had when the drive was turned on. So you grab some planets from opposite ends of the galaxy, and thanks to the expansion of the universe, they’d fly at each other pretty much at the speed of light. Okay, geek mode off now.
He used this in one or more of the Ringworld books too (they use it to get back to the ship buried in solid rock.
The Wave-Motion gun from Star Blazers. That thing was just rad.
The Light of Judgement from Final Fantasy 6. I don’t remember if it could take out more than one person at a time, but still…
And no shields, hyperdrive, or internal life support. Those things were flying cardboard boxes.
You want a REAL Star Wars starfighter, you go with the TIE Defender. Or an E-wing.
You guys know what else was a really cool weapon? The Tembler Bomb, from Wing Commander 3. It was a fighter-mounted missile that, when fired at a sufficiently tectonically-unstable planet, would cause the damn world to shake apart at the seams. It’s even cooler to hear it described by John Rhys-Davies…
Damn, that WC3 ending movie was awesome…
Oh, and let’s not forget the joygasm-inducing PPC’s from the MechWarrior series. Hell, you load a pair of those onto a Mech, match it with some LRM-15s or 20s, and you’re golden, baby.
I’d like to nominate the Harpoon Gun from the computer game “Messiah”.
There is something unbelievably satisfying about a gun that detonates a powerful explosive to propel a large harpoon at such incredible speeds that it makes the target airborn untill it embeds itself into a wall behind the target 
Oh, and the people usually survive for a while, suspended by the harpoon somewhere and screaming for a quick death. Oh, the glory
— G. Raven
The light grenade. I’d love to leave it laying in the middle of my work, the place would be vacant by the next day (From “Mom and Dad save the Universe”, IIRC).
My favorite would probably be the ACVs (Autonomous Combat Vehicles) from Albedo. Space-based missiles, about 3.5x12 meters in size, and likely a couple hundred tons, with a neural-net computer, and a fussion engine. They could either be given specific directions to follow through, or sent to act on their own as needed. Very smart missiles. No warhead, though, they relied on pure kinetic energy to kill. Not exactly the most elegant or flashy weapon, but when you can smack a target ship or planet with a few hundred tons of metal traveling at a few hundred or thousand KPS, it’ll make quite an impression
And I like the Ogre, too. Nasty little (Hah!) thing there, isn’t it? 
And of course, the M41A1 Pulse Rifle, M56 Smartgun, and Sentry guns from Aliens. Cool toys.
The Zenade from Alan Moore’s Halo Jones Comic strip series. It’s a grenade that detonates with an ‘AAAAAAAUUUUUMMMMMMMMMM’ and makes everyone in its blast radius incapable of anything except oneness with the universe and introspection.
Damn, I’m pissed you beat me to it.
I love the variant he threw in during Children of the Lens where they travelled to a parallel dimension where the maximum inert velocity was about 15 times the speed of light, freed a couple of planets, brought them back and flung them at the Plooran base. It was even cooler the way he described it. To paraphrase: “…Hmm. Instruments went dead, star went supernova and a hundred years later our scientists are still scratching their heads…”
Some other Smith greats:
Fortifying entire planets, slapping a Bergenholm on them and just moving them to where the fight is.
The Q-Gun. Need I say any more?
The dureum space axe. Love at first site. Able to cut through anything like nobody’s business. More specifically, dureum space axes plus armored Valerians (big men of Dutch ancestry who grew up on a high-gravity world).
Outside of Doc’s books, I’d have to say the Shadow planet killer is a personal favorite. But that’s already been mentioned.
Vernor Vinge had a character in Fire Upon the Deep who had a battlesuit with nanotech drones. Way cool. In the sequel, those spy cameras Pham was using to coordinate the battle were also pretty awe-inspiring. I also loved the lasers on those ships in the sequel. One of the few times in sci-fi where an author actually treated a laser like a laser, instead of as a really pretty normal gun (e.g. worrying about burn and linger time, energy transfer rates, etc).
Well, Badtz beat me to the Soft Weapon, artificially intelligent, mass-converting, handheld city/civilization killer that it is. So many of the good ones are already taken…hmmm…
How about a (primarily) defensive weapon from the worst-named sci-fi novel in many years…the Krang? A musical instrument that maintains a nigh-impenetrable shield around a planet and creates singularities inside targets. No fuss, no muss, no warning–ships just wink out of existence. Of course, it’s a little difficult to fire…
Another one worthy of mention is the particular Bolo from Mercedes Lackey’s “Operation Desert Fox” short story. RML-1138 (“Rommel”) isn’t just any Bolo–it’s a fanatical student of the career and tactics of Erwin Rommel, one of the greatest tank commanders in history. So in addition to the raw power of a Bolo, it’s made itself a master of armored tactics and command.
Dammit, and I also forgot Doc’s Sunbeam. Gathers the total output of a star and focuses it into a beam of light. Whatever it hits doesn’t exist any more. Good clean family fun.