EDIT: I now realize I just regurgitated what you guys were saying up top.
I might be off base (and if I am I'm sure you dummies will let me know) but I think the way to do this might be with overall hitter PA. I just joined a $160M DH league that just posted the schedule. I have the least in my division at 6248 PA, the other teams have between 6500 and 6800 PA. I'm in SafeCo and the other division parks are Astrodome, Robison Field and Municipal. Pitching is great throughout but I think I'll be fine running at 95-98% by the end of the season. I've got 6248 x 110% for 6872 PA before I hit a drop in the fatigue percentage. At 95% a player is on pace for 15% more than RL PA. 115% gives me 7185 PA. That's between 42-44 PA per game which should be enough, I'd have preferred a division full of SafeCo, PetCo, and ATT.
I understand this is totally gaming the system, but I'm good with that. Baseball has always been about gaming the system and exploiting the rules.
Anyway, in my mind, the primary controls (or uncontrolled factors) for a fatigue challenge are (1) overall hitter PA and (2) parks. Secondary controls would be (3) pitching and (4) whether to have the DH.