I'd like to see something along the lines of an electrolaser, only 50s style. Basically a lightning gun that could have bonuses against robots and such. I'd really rather not see any modern assault rifles beyond chinese made AK type weapons. The M16 type assault rifles can't last 5 minutes in iraq never mind centuries after a nuclear war. Plus they're cheesy, dull and overused beyond belief. More 10mm pistols, fewer G11s.
In defense of the Fatman (yes, yes, I know), there are a couple of manners in which it could be used that make some vague sense. Judging by the size and probably weight of it it was designed for use by power-armoured troops. Since the FO universe diverged after WW2, we can assume that they stuck more to the old style battle tactics than more modern ones. The Fatman appears to have about the power of a mortar (from the size of that explosion) with some added radiation. A mortar weapon that can irradiate a small area and be carried by troops rather than towed about would be immensely useful for clearing out trenches and fortified positions, especially if your troops are wearing power armour, which gives them massive protection against radiation. Of course, that's only a reason for why the Fatman could have been developed, not how it will be utilised by Bethesda in Fallout 3.