In Dark Messiah you had an ability called adrenaline that allowed you to instantly kill an enemy. I played rogue, and a skill branch was the ability to use this multiple times.
I simply used it on every boss, even the final one! I just hit him with a knife twice and he died. Though, I beat the game several times and this only worked perfectly on my first run through.
I also killed the final boss of Borderlands by hiding behind one of his tentacles and just shooting it a million times with my shotgun.
Also, to kill the final boss of Half Life I jumped into his head and shot his brain a million times. Though, I think this last one is the only way to beat him?