I have to say Deathclaws from Fallout...they can kill you in one hit and they have insane amount of health, not mention their insane speed and the only place where you can get the Vengeance in Fallout 3 is in a place infested with em. you have to fight through hordes of them, only to go underground and find more to fight through, by then you're either out of ammo or you got hit by one and managed to live through it.
Sigma from Megaman X4. The battle it proposes is so lame... Yet it's nearly impossible to beat. What a waste of time (and lifes) just to watch him say he'll be back for... 5 games with the same formula.
Hmm...NANCY-nq342onjogenof-whatever gets to my list. You just have to keep hitting it, yes, but it's laser is freakin' annoying. It's a ROBOT, is AIMING AT THE TARGET part of its programming? at least it would've been easier if that was the case.
The Infant Necromorphs and those bunch-o'-meat-for-a-necromorph