I support the idea, but it really depends on how you fly the game. I like long patrols and I've flown multiple-hour sorties without time compression. Mentally, one is tired enough after that. One ends up making poor decisions and maneuvers lazily.
Fatigue modeling would really only affect those used to quick TnB action in sorties lasting under ten minutes. Furthermore, everyone is different, and applying the same fatigue model to every pilot might cause an uproar among those who believe they're stronger
Physical fatigue relates to mental fatigue, and flying will tire you both ways, but it's not always the case in a computer game. Putting an alert mind (player) into a fatigued body (sim pilot) will probably just induce frustration.
But if it's an option, why not?
A hypoxia model would be cool, but it would require modeling of some O2 systems. Pilots had to check their masks for ice buildup and could squeeze the hoses to test if oxygen was flowing. In Il-2, none of the O2 guages are even functional, just static eye-candy. O2 systems would also need a DM, and this might be even more complicated in pressurized aircraft (the entire cockpit skin would need hit-points, I imagine).
In terms of latent stresses on pilots and aircraft, it's my opinion that it would be more important to see some effects of accumulated damage to airframes, engines, and weapons as well as random failures. With Dgen under revision, it would be great to see something like historical dates and theatres affecting probability of failure as well as how the plane is handled from mission to mission (ie G-force stress on airframe accumulates throughout a career). It won't be popular to everyone, but again, it could become an option.
One member posted a while ago, either here or in the Clod forum, that because aircraft performance could vary depending on manufacturing conditions, that aspects of performance such as top speed, G limit, maneuverability, etc should be randomly assigned to within about a 5% margin of accepted performance figures. One mission you could be flying a top-shape hot-rod, and the next you could be assigned to the squadron beater, and not really know how the plane will behave until you fly it. It could make things interesting and possibly change the scope of "this plane should always be better than the other" discussions.