The most infamous choice on the list (well, outside of the one in Infamous--hey-o!) is the ending to Mass Effect 3. You've probably heard jokes and read forum post after forum post about how this was the suckiest bunch of suck that ever sucked. Opinions on the quality of the content aside, the in-game choice Shepard has to make here is, for lack of a better term, pretty shitty. Those who defend the ending maintain that having only bad options is an artistic decision--sometimes, things just suck. Not every choice has you ending with you consorting with aliens.
You can choose to have Shepard take control of the synthetic Reapers, fusing his mind and soul with them but killing his physical body. You can choose to destroy the Reapers, but unless you did a ton of prep work and side quests, Shepard dies in the ensuing Citadel explosion. There’s also sacrificing Shepard to fuse organics and synthetics together into a single, galactic master race, or just being a petulant child and doing nothing, thus restarting the cycle of destruction. No matter what you choose, the character you've been grooming over the entire trilogy won’t make it out, and while heroic, it also really sucks. Thanks for everything Shepard, time to die now.