This may suprise a lot of you: Fully-modded Laser Rifle is my answer.
Most threatening things in the game are Cazadors or other pack-like creatures that move quickly, or Deathclaws, which are basically big-hitters. The fully-modded laser rifle has it all: the firing speed, the scope for precision, the crit damage (first hit is basically always a crit when sniping due to the sneak attack mechanic, and a crit from this will be 66 damage), the massive clip size (this is probably the single most underrated weapon stat; this is the difference between life and death a lot of the time) and it's damage is beast vs. non-armored pack-like enemies from the get-go. Only downsides whatsoever are that you'll want AT LEAST either Laser Commander or a crit build or it'll suffer vs. armored foes. Oh and of course you'll probably want to cope with the sheer weight of MFCs one way or another. But yeah, any character I have that uses THIS weapon? His survivability goes up three-fold. So deceivingly simple and cheap, and yet so undeniably powerful.
So there's my answer. How about yours? Which weapon do you consider to be -the- most overpowered storm of death the game has to offer?