Imagine an the Au where something went horribly fucking wrong with the Monokuma virus, and not only did it physically manifest as a Monokuma, but it caused problems with Usami's programming; so when she tries to fight Monokuma for the first time, it causes her system to corrupt and his to be fixed, so they sorta swap coding objectives. I say coding objectives and not personalities because it basically the monomascot version of the different Mastermind aus.
As a result, you have an evil Usami running the killing game, and a good Monokuma on your side trying to stop her. I don't think it would change much of the game itself as it would just character interactions between Usami, Monokuma, and the Ultimates; unless you wanna think about how twisted Usami could be as a headmaster.
just a thing i had in the back of my mind