Newcastle in my current save. They have an Irish regen who is pretty much the perfect target man - 6'7", superb touch for a big man, intelligent and creative. And if that wasn't enough, Lukaku. The rest of their team is pretty average for a team battling for the top 4, but those two always seem to lose their markers and stick two past me no matter what I do. My record against them is actually decent, I just always get a feeling of dread when they're up next.
In my previous save in FM11, it was Lyon, after I moved to Nantes after getting tired of winning everything. I picked up more than my fair share of victories against PSG and OM, but I never won against OL in about five seasons in France, and I'm not sure I ever even drew. They just had a brilliant team - a 6'8" target man, a pacy two-footed goal poacher, great defenders, a midfielder who could score from anywhere - to rub it in, most of their best players I'd previously managed at some point in that save.