Most irritating single achievement .I have is probably One With The Shadows in Alpha Protocol
Complete 3 missions without being detected or killing anyone (tranqs and unarmed stealth knockouts are allowed).
It wouldn't be so difficult if there were more then just a few missions in the entire game that you can actually get credit for them in (There are 5 total, and 2 of them are right at the beginning of the game before it's possible to get a ridiculously high stealth stat, and one of them has a "Boss Fight" encounter at the end that I'm SURE is only possible to complete and get credit for the achievement is you abuse some of the mechanics of the game (which I did, it still took me about 5 hours of trying to beat that last room without being detected - notably it involved pistol sniping a guy with a tranq dart in the head and then running away and letting the enemies reset.. they don't necessisarily reset to the same positions that they were in when they were all there, so you just snipe the closest one, run, come back, and hope there's a guy close to snipe. Not really cheating, but not really in the "spirit" of the achievement either)
And, occasionally an enemy will see you just before you knock him out, but he won't even show that he's been alerted. You'll think you did the mission perfectly, but you didn't, and you won't know until you complete the final mission that it's possible to complete it on and NOT get the achievement, and then have to load an earlier save. I had to start the game over several times because of that trying to get this achievement.
I did it though. Of course, there MIGHT be easier ways to do the mission, but it's still very tense and annoying, and the glitches littered throughout the game make it all the more difficult.