I'm gonna get yelled at for this one, but it is, and always will be, until it is yet again nerfed, the bloody sticky spam. UGH. I honestly feel that the only people who complained about the air-burst stickies getting nerfed were the friggen demomen who relied too heavily on that strategy in the first place.
That and Half Zatoichi when it gets random crits.
Also, when someone has an unusual hat/australium weapon W/ Professional Killstreak effects combo, and actually has the skill to back up their pompousness. I usually target them first, but when they can actually beat me I get angry >:I