Aside the times I've left games for personal reasons, like lack of time, playing on too many games and needing to cut back so I can give specific ones the fair shake they deserve, and so on, almost all of my leaves have been over unethical staff behavior.
I'm right there with @Gilette giving Multiverse MUSH as an example of so many things being wrong in one place it's a wonder we don't have more of their former players here. Staff abuse of the suspect flag, staff targeting players for posting here, discrimination by staff and "elite" players of the lesser folks, loud minority players making the game unfun for everyone else, a staff member (Lord English) being caught having modified gripe logs to alter their context and outcome being protected by current and former headwizs, whisper campaigns being run by staff and high-ranked players alike, the promotion of unsuitable, provably malicious players to positions of power (Priscilla etc.), staff favoritism and the list goes on.
I left Brave New World and Fallout: El Dorado over Elsa being Elsa. I think that's a sufficient reason.
Sexual harassment being tolerated by staff is also something I'll leave a game over. United Heroes comes to mind as the latest instance but I feel every other WoD MUSH ends up going that path for some reason.
On the subject of WoD games, I've been known to leave ones that start relatively small or constrained, i.e. Vampire or Werewolf, but then decide they want to introduce three or four more splats in one shot in an attempt to attract more players. Speaking more broadly that's a red flag for me. If your game has a "soul", a "feel", and you throw it away in a transparent attempt to appeal to larger masses, I won't stick around. I only ever join a new game when the core idea appeals to me. If you discard it, you've taken away the reason I joined, and I find it an almost universal fact the new core of the game won't be as thought out as the old one.