Overall best: Firelance
- It requires an event that you need almost full Luck on, but it scatters the Firelance and 21 Alien Power Cells. From that you can tell that the Firelance is an Alien Blaster: it is named the Firelance because it has the added effect of setting enemies on fire. It can also be upgraded with Better Criticals AND Pyromaniac.
Highest damaging: Experimental MIRV
- It's really expensive and there's only one, but the MIRV is the highest damaging regularily obtainable weapon in F3, firing 8 Mini Nukes at once. No more, no less. If you don't have eight Mini Nukes, it just clicks eight times. It is recommended to use it at level 16+ and only in VATS. Regular fire will kill you.
BEST WEAPON EVER: Mysterious Stranger's .44 Magnum
- If you have the Mysterious Stranger perk, every once in a while during VATS this guy comes up and kills everyone. His weapon is a custom Scoped .44 Magnum with its own ammunition. If you get it, it does 9000 damage (perfect excuse for a meme here) and also has a 100% critical hit chance. The crit chance is a bit overpowered, though, because it still kills practically anything in one hit (except a modded Super Mutant Behemoth with 10000 health, and even then it might kill it).