A few problems that have remained persistant over the course of the game (all the way back to vanilla).
Any time a new patch or update releases, my options get completely reset. Every time, I have to remember if it was X or Y axis that I had inverted and it takes a bit of time to figure out which way it actually was that doesnt feel wierd. Generally setting up all of my key binds gets extremely tedious and irritating. Somehow, my achievements remain, thankfully.
Within the online lobby, it says that there are X number of players on, but I cannot see anyone in any of the lobbies. Oddly enough they can see me and communicate with me.
Now, upon writing this, I've forgotten many of the issues that have plagued me (many have actually gotten resolved over time). I'll have to play through a full game with some friends in order to remember, but those two above were what I remembered and tested just now.