Every fucking Spartan in Noble team.
Nothing has been more ferociously annoying than playing through on Legendary with those retards.
I'd find myself just chasing them through the levels beating them with whatever weapon I had until they'd actually do something.
Normal marine NPCs can be excused for being useless, but Spartans?! They should know better.
EDIT: Also, those damn beggars in Assassin's Creed? Agreed. Similarly to Noble team, I would forgo entire pickpocket missions if one of those ruined it for me and beat them into the dirt.
EDIT EDIT: Guild Wars NPCs. All of them. Whenever ANY NPC in that game (looking at you, Mhenlo) has to survive a mission, it's a guaranteed fail. If you've played this, you'll know how freakin' suicidal they are. It's mindblowingly annoying.