Gotta mention Deus Ex: Human Revolution, the original version. Early in the game your biochip starts experiencing glitches, and there's a small optional quest to replace it. Fast forward to the end of the game and, guess what? That glitch was actually the illuminati trying to force augmented people to get a new chip they can control with a kill switch. You are now fighting the hardest boss in the game with every augment deactivated.

Oh that reminds me. Not a final boss issue as much as it was an every boss issue but that is something that bugged me about Human Revolution when it first came out. You could do a full pacifist run except for the bosses. They ended up patching it so you could complete a full, actual pacifist run though