In order: (I've limited myself to 1 weapon per series)
1. Cerebral Bore (Turok 2)- sorry, but a gun with locks onto an enemy, sucks his brain out and blows his head up cannot be critised unless you have a weak stomach.
2. Ion Cannon (UT/CnC)- I just like the concept of bringing down 12,000 megawatts of power to kill one guy, adds whole new meaning to the phrase 'overkill'.
3. Railgun (Red Faction)- 1 hit kills, almost perfect accuracy and the capacity to shot (and see) through walls made this pretty much the only sniper weapon I've grown to love using.
4. Wrench (Bioshock/System Shock/Prey)- Misuseing tools for violent purposes have been a staple part of FPS games for quite a while.
5. Serious Bomb (Serious Sam)- I just can't resist anything with the nickname of 'the Atomic Firecracker' and also it is painfully powerful.