My vote goes to the Kleer, from Serious Sam, and apart from maybe, MAYBE Cliff Racers, I dare you to play that game through and at least not partially agree with me.
In a game with rapid-fire rocket launchers, enemies who have bombs for hands, and giant demons a thousand times taller than your character, undead cows (one of the first enemies in the game, mind you) are worse than all of them. At least 50% of my deaths were from that one enemy alone with a variety of at least fifteen or twenty.
Jesus Christ. I can still hear that clacking noise they make when they run at you, and the stupid grunt they make when they lunge. Basically, all you could do was curse and wait for the minigun and the laser. And the grenades. Sweet Jesus, yes, the grenades were like Kleer-pwning Nirvana.