Assuming ultra-tech sci-fi stuff, a modified Star Trek transporter. It can be used in a couple different ways; For a point target, simply use the transporter on a person… But never re-materialize him. Scramble him into raw energy, never save his pattern. For an area target, you start the same (Disintigrating the target into raw energy), but then just don’t do anything with it. Doing that, you could “transport” one kilogram of matter (Say, a brick) out of the white house, and flatten all of Washington with the released energy. Or for a slight twist, transport a 1-kilo weight from your ship/base/whatever to the target… And simply “neglect” the final step of re-constructing that energy into matter. Same huge yield, but you don’t need to transport anything away (Or, for the ST universe, you don’t need to transport through their shields).
Star Fleet could be vicious if they just had some creative minds in R&D…
For more real-world stuff, I think the nuke is it. At least for now, and I doubt nuclear weapons will ever be considered below the level of at least runner-up for the “Ultimate Weapon.” I can only see two contenders for pure destructive power:
1: Antimatter weapons. Very small compared to an equal-yield nuke (Most likely, that is). And since they do not have radiological matter like a nuke does, it leaves no fallout (Though they do have a significant burst of gamma radiation on detonation). However, it’s not safe to handle, to say the least. It’s almost like using nitroglycerin grenades. Sure, they’d be devestating. Just don’t jostle it too hard. In the case of antimatter, if the containment failed, you’d have a full yield. Not exactly what the millitary would consider a very good thing, since the emphasis lately among the higher-tech millitaries has been more redundant safety systems for manned vehicles. It also takes a huge amount of resources to produce…
2: High-mass/velocity kinetic-kill weapons. Take an asteroid, strap a high-power rocket on it, and accelerate it into the Earth’s gravity, at the proper speed to impact on the point you wish. Or if you wanted, maybe manufacture 100-200 ton missiles like that, just a rocket, fuel supply, guidance system, and a few hundred tons of armor on the front. Systems like this would be slower to deploy than nukes (At least, untill systems like the NTR are developed enough), but carry similar devestation, and with no fallout or radiological effects (Except for a small microwave pulse upon re-entry, IIRC. Though a NTR would introduce -some- radioactive matter into the mix, not that it’s stopped anything in the past, Ex. depleted uranium ammunition). Without the highly radioactive nature of nukes, and without the negative association nuclear weapons already have, I can imagine they would be much more likely to be used than nukes would, too…
But this is also assuming just direct weapons. Biological weapons can get especially nasty. Engineered viruses (Or possibly even nanotech “viruses”) could be more devestating. Boost up the reproduction and contagiousness of a virus, as well as making it resistant to mutation (If possible), but make it non-damaging under most cases… Then give it a trigger. Make the trigger whatever you’d like; A set time, some rare but harmless chemical, a certain string of enzymes, etc. Just give it enough time to spread through a population, then introduce the trigger; The triggered virus triggers all the others that it comes into contact with (Maybe it excretes that enzyme once triggered, or something like that), and the entire population gets sick almost simultaneously.
