Well, Tapioca Dextrin beat me to it, but my favorite weapon by far is the Gravity Gun from Half Life 2.
“You can call it a zero point energy field manipulator, if you really want to. We designed it for handling radioactive materials, but we mainly use it for heavy lifting. it comes in handy for clearing out mine fields.” Yeah, not to mention sending buzz saws through headcrab zombies and hurling grenades back at Combine soldiers. 
Vash the Stampede’s angel-arm. There’s a reason they call him the humanoid typhoon, y’know…
As I remember, they’re called Tachikoma in the anime series, but were Fuchikoma in the original manga. (And I don’t speak Japanese, so I can’t tell you what signifigance the name change has, if any.)
Sharks with frickin’ “laser” beams on their heads
or Ka’ D’argo’s Qualta Blade/Rifle
Specifically, the Twenty-Second Bomb. In the opening scene, the protagonist throws this into a building full of aliens, he figures it’s a church. It recites, in the alien’s language, “I am a twenty second bomb. I am a nineteen second bomb. I am an eighteen second bomb…” Better even than the nuclear hand grenades, if you ask me.
I’ll also add:
The hammer from Hexen. There’s never any reason to use anything else as a Warrior. High-damage, cheap, explosive ranged attacks, and even unpowered it can still kill in two hits at melee range.
The two-barreled disintegrator, from Ringworld: The disintegrator is a digging tool; it fires a beam which suppresses the negative charge on the electron, causing solid matter to dissipate into a monatomic powder. The two-barrelled version can also fire a separate beam, which suppresses the positive charge on the proton. Both beams should not be used simultaneously, or a current would flow.
The lightning sword Alric (briefly) uses in Myth II: Soulblighter. Cutting down a Myrkridia in two swings is good. Cutting down twenty Myrkridia in two swings is better.
The Six-Fingered Sword, from The Princess Bride. The best sword since Excalibur, and made for the peculiarities of a single man’s hand… that single man ultimately, of course, being slain by it.
The Sickle of the Valar, from The Silmarillion. See it, right up there? No, to the north.
Also from The Silmarillion, the knife Angrist, iron-cleaver.
I think the ability to do the Vulcan nerve pinch would be pretty fricking sweet.
And how about some sharks with lasers attached to their heads?
Fembot
LIght Saber
God, I’m really a pathetic geek.