The problem I have with Mewtwo is that in the games, it is a wild pokemon, and there's no indication that anyone ever recaptured it, whether Team Rocket or otherwise. To say the plot started with Mewtwo escaping Team Rocket implies that Team Rocket had it in the first place here. Also, it's the very lack of characterization of Mewtwo in the games that concerns me- all of the information that IS given indicate that it's a vicious, ruthless mutant. Look at its pokedex entries across the generations, there's nothing that suggests that game!Mewtwo would even bother with any elaborate schemes, that's an invention of the anime and Special. In fact, the games basically never suggest that Mewtwo is particularly intelligent or cunning, just powerful and vicious. So while I could see an event being based around Mewtwo rampaging or something, it's hard to imagine a game-verse plot with it pulling something like this.

With that said, the plot idea sounds interesting in general, if you take out the Mewtwo element. Honestly, I think it would work BETTER without Mewtwo being involved, as Mewtwo comes across feeling like a deus ex machina, but that's just my personal opinion.