I wouldn't say the moderators are the main cause of 4chan fatigue, it's more like too much focusing on mod channels. I've butted heads with them plenty of times because I keep vainly hoping to push my ideas about how the site should run.
There was a point before I came to terms with it where I kept getting frustrated at no one caring about my special opinions and I wanted to quit, but the problem there was just me being too ambitious and trying to do too much with none of the tools or titles. Suddenly having access to the admin's/manager's ear anytime makes a lot of us think we're more important in decision-making than we really are.
I know this has unfortunately brought out the government lobbyist in me, and I think a lot of us are guilty of the "if mommy says no, ask daddy" tactics and strategic badgering of mods to get something done. I think jannies with strong opinions tend to burn out quicker because of this. Nobody comes in expecting to be asked for advice, but when a mod replies to you once or twice it can make you feel stone-walled when you get ignored by them later on, and it makes you wonder why you're putting effort in at all.
I don't think like this anymore, of course, but there was a point where I was trying to get some policy change i wanted and i wanted to give up on everything.

In any case, besides being defeated by one's own hubris, i think the biggest thing is just time allocation. Situations change and suddenly you can't sit at a computer for hours at a time anymore, or maybe someone's looking over your shoulder now.