The writing making the characters repeatedly try and display how smart they are (which I'm aware is integral to the show) but to me makes them totally and desperately unlikable. That, coupled with the general tension building component of most sit-coms where all too frequently characters do what is clearly a bad idea, followed by some form of "make it better" set of actions.
I know that if they [the characters] made a mistake and just repaired it in a very mundane way this would not be good television, but I find it incredibly jarring that these unlikable characters have one thing going for them, their intelligence, yet seemingly couldn't find their way out of a paper bag.
(EDIT: This reflects the relatively few episodes I've seen, but every time I see one I feel exactly the same)
(EDIT2: Perfect example from a comment below,
"When he [Sheldon] drops some furniture he is carrying to debate the point that pulling it up the stairs would reduce the required vertical force by exactly fifty percent and not about fifty percent, he is doing something weird and nerdy..."
Debating yes, absolutely, but scientific debate by itself isn't funny to the general population (Deestan would enjoy it, I might enjoy it, but Joe Bloggs on the street probably wouldn't care) so he drops it. That's not smart. If the show was consistent he'd then point out that the loss of energy from dropping it far outweighs the benefit of moving it around, or he'd break his toe.
It's this orthogonal slapstick which seems totally incongruous with Sheldon's typical behavior which annoys me.