Boss fights. Sometimes they work, sometimes they don't. The end boss kinda messed up the ending to Bioshock, I feel the game could've been better without it. And the boss fights throughout Deus Ex Human Revolution were terrible, same for Alpha Protocol.
In System Shock 2 it was even fairly easy to end up in a situation where it was impossible to win the final boss fight, because there isn't a single ammo vending machine in the last two levels of the game AFAIK. And she's immune to one of the melee weapons.
I'm pretty tired of most boss fights myself. Largely because it's such a predictable format now. "walk around, do stuff, oh look here comes the boss fight." Repeat.
I'd rather have a steadily increasing difficulty of fighting, with act end or important plot fights being difficult for some other reason besides "they have 600,000 hit points when every other enemy had 3,000" and/or you're locked in a room/arena with them and they have some kind of instant death attack.
I'm still not entirely sure what could replace them, tho. It would just be more interesting if I felt like there was more strategy involved than running over and trying to beat/shoot/spell a single foe to death while strafing in circles with maybe occasionally ducking for cover a couple times.