Penny Arcade Adventures/YMMV

Goddamned Boss: The vampire mime and the final boss. All enemies attack faster than your special attacks can charge, but these two can attack at least three times in that space.
- The mime is bad because its attacks have a very short block window, requiring near-perfect reflexes to manage a solid block. Getting a partial is often the best you'll manage, which means you'll spend half the time suffering from an attack debuff.
- The final boss is easier to block, but attacks a lot more than the mime does and uses area attacks exclusively until the final phase. Once you hit the final phase, then it gets cheap as hell by spamming a single-target attack on Gabe several times in a row, occasionally doing it twice before Gabe can actually hit back.
Scrappy Mechanic: Blocking, which is easy half the time and unbelievably difficult the other half. Against some robot attacks, blocking is literally the difference between Scratch Damage and a One Hit KO, and these attacks occur almost instantly. This gets better as your level increases, allowing you to tank a few non-blocked hits, but not by much. The sequel was a lot better about it, both in blocking being easier and having enough health to survive regardless.
- That mini-game you have to do in Episode 2 when you're thrown into the asylum. If you don't like puzzles, you're going to have a rough time with that. Especially since, do to the randomized nature of the puzzle, it can literally be impossible to complete on some iterations.
Squick: There are several buffs which involve urine, one of which your character takes intravenously.
That One Attack: Any status effect attack counts, since you can only have one active at any given time, but attack reducers take the cake. Unless you wait it out or rebuff, it takes you out of the fight until you wait the effect out. The vampire mime is especially bad about this, since its Wall of Hellfire attack is nigh-unblockable and gives said status effect.