Never ending bad beats and coolers.  It's what made me quit playing poker, after playing it for around 5 years.  It was like my second job.

For a time I thought I was doing fine, winning here and there at small to mid stakes, playing a lot and continually studying the game trying to be better at it.  Then one day, I just stopped winning consistently anymore.  And I couldn't explain it.  Maybe it's the game evolving and moving too fast for me to adapt, or maybe I was just running good and the poker gods decided to turn off my run good switch.

But then one day I decided enough was enough.