For me it's difficulty through bad mechanics and/or glitches. Typical situations where I stopped playing
- realizing I had gone past a point of no return before I was ready for it, but couldn't be bothered to load a way earlier save
- getting stumped because I had missed a major upgrade/better weapon/etc and couldn't be bothered...
- finally beating a difficult boss only to find out every level onwards will be populated with it's siblins
- running into a section inconsistent with the rest of the gameplay, for instance a long, hard stealth section in the middle of a trigger-happy shooter
- dying for the umpteenth time in the same spot by falling into a pit of insta-death, getting shot by an invisible enemy or getting stuck in the geometry
- realizing I had gone past a point of no return before I was ready for it, but couldn't be bothered to load a way earlier save
- getting stumped because I had missed a major upgrade/better weapon/etc and couldn't be bothered...
- finally beating a difficult boss only to find out every level onwards will be populated with it's siblins
- running into a section inconsistent with the rest of the gameplay, for instance a long, hard stealth section in the middle of a trigger-happy shooter
- dying for the umpteenth time in the same spot by falling into a pit of insta-death, getting shot by an invisible enemy or getting stuck in the geometry