Definitely any protect quest in any game ever, with the possible exception of Ico. Prince of Persia: The Sands of Time suffered from the flaw, and it led to no end of frustration. Although the fact that I never mastered the combat in that game may have something to do with this.
In terms of RPGs, random battles every three steps is the most frustrating thing I have ever experienced in a video game.
In God of War: Spoiler: The last three bosses really put a damper on the game as a whole, I thought. Between Ares' unblockable, super-quick, out-of-nowhere, massive-damage attack that was used every three seconds and another bloody protect quest against a thousand versions of yourself, I had to turn the difficulty down to finally finish the damn thing. And that is a pain on the ego, I'll tell you that.
Also, there was a bunch of stuff in Spider-man 2 that was broken and needlessly infuriating. Any battle with Mysterio, for example.
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