MCU X-Men
I'd introduce after the dust settles from Thanos, and use the mutant question to frame themes of personal responsibility. Without getting too heavy, adolescent mutant powers are actually a pretty scary thought. Young people having access to things that would make our current juvenile violence epidemic comparatively small potatoes is something that I think Xavier would recognize and whose potential he would be be tremendously afraid of, so he's pulling mutants from society and keeping humanity totally in the dark through memory wipes and manipulating perceptions. Xavier's School does not train crime fighters, it isolates them from a world that Xavier is convinced would hate them, if it knew they existed. He trains them and is the protector of mutant secrecy. Sort of pre-emptive avoidance of mutant registration and all that.
However, this leads to a lot of personal turmoil for kids (some of whom are passably human) who want to interact with the world and are confident in their abilities to handle their mutancy responsibly. They don't like being on lockdown, basically. Ultimately, they'd convince Xavier that it's unethical to keep mutants hidden, even if it is for the greater good.
Of course, you need villains who lend themselves to these themes but are not Magneto or Mystique. I'd go with X-Cutioner, as an FBI/Shield/Whatever Agency agent who cottons on to the the secret mutant menace and steals a bunch of tech to kill mutants with. He finds out about Xavier's School as the turning point in the second act, when the burgeoning X-Men rescue a target of his. Secondary villain would need to be someone who operates on a massive scale, forcing the X-Men into the light of day (Juggernaut, probably, especially as he would lend and additional personal conflict to Xavier's narrative).
Teachers:
Xavier (limited screen time, he's sort of the Dumbledore of the film)
George Clooney would be my longshot, but...
Kyle MachLachlan is more realistic.
Storm (the Iron Man sized role)
DeWanda Wise
Beast
Sean Astin
Forge
Tokala Clifford
Kids:
Shadowcat
Hailee Steinfeld
Cyclops
Blake Jenner
Jean
Lily James
Iceman
Nick Robinson
Rogue
Eiza Gonzalez
X-Cutioner
Jon Hamm
(Future Characters: Daniel Craig as Magneto, Travis Fimmel as Sabretooth, Dane DeHaan as Toad, and Christopher Abbott as Wolverine)