Hal and Lois are the two that most frequently get on my nerves. Their horrible parenting, their whole love thing is WAY over the top, and I'm SO glad we haven't had to see any more of the Hal naked/body shaving scenes which were totally feral.
Malcolm, he doesn't get on my nerves, but last season I found his storylines started getting boring. The diving board subplot in the most recent episode was so tedious I was glad I was watching the downloaded version not the TV version so I could skip those parts.
Jamie, there's nothing annoying about Jamie apart from all his appearances being way too brief, that is if they even have him in the episode at all, I reckon they should use him more.
Dewey, the same, I reckon they should show more of him and the Busey class, because that is a great subplot. He on his own has funny moments too, like how he started singing the Meow Mix song in whichever episode that was, can't remember now. I don't find him annoying.
Francis, I'll leave him out because we hardly ever see him any more, mind you I found a lot of his storylines over the last 2 seasons boring as well.
And Reese, what annoys me about him is his 'dumbness'. While he can be funny, at the same time he can be annoying - or EXTREMELY annoying as he was in the Experiment episode.