I like putting myself into fights where I'm outnumbered 2 to 1, it's such a great feeling when you come out on top of a fight where the odds are stacked like that. I also like turning down the attack damage and turning up the damage resistance of everyone in the fight so that they last really long, sometimes upwards of eight minutes, even. During these fights, however, I notice that even after eight minutes the combatants are still fighting with the same speed and strength that they were at the beginning of the fight, and I thought that was a little unrealistic.
Obviously this game isn't supposed to be hyper realistic, I don't expect to see anthropomorphic rabbits fighting in the streets anytime soon, but personally I think it would be cool to have that extra level of realism. It would make fights last longer, even with the default stats on characters, add a level of strategy to combat (i.e. choosing when to strike multiple times, having to stop and breath etc.), and could have some interesting/comical effects when both people in the fight have to stop and breath for a moment. The fatigue would make characters attack slower, do less damage, not be able to block as easily, and it would make fights where you're outnumbered that much harder because you have to wear down two people as opposed to just one. It's a lot like the hallway fight scenes in Daredevil and Oldboy, the protagonist has to keep fighting, even though they're worn down and on the verge of passing out and the other fighters are still on top of their game.
I don't expect everyone to embrace this idea, because it will significantly affect one of the main reason's they love the game so much, so in the character stats menu thing there could be a check mark named "Fatigue" or something, that way if they don't like the feature, they can just turn it off and go back to the way combat has always been. Anyway I think this would be a neat addition to the game and add that much more variety to the fights, not that they need it.