UT2004: Shock Rifle, definitely (in InstaGib mode) or else the Flak Cannon in normal mode.
Q3A: BFG!
Is there anything better? (I especially dread that whooshing sound when I hear it and when I see a green glob heading towards me, I know one split second before it hits that I am doomed even if it falls anywhere near.)
HL2DM: Gravity Gun, obviously. Nothing like hurling explosive barrels at someone or inserting a plug into an electrical outlet and watching some poor soul get disemboweled at the other end.
CS:S: UMP (CT) and the SG-552 Commando (T)
Tribes Vengeance: DA Jackal Sniper Rifle and the Mortar Launcher (muhahaha, talk about sheer power!)
D3DM: Plasma Gun, most definitely!
Painkiller: Rocket Launcher, especially in the People Can Fly and The Light Bearer modes.