Oh right, there's Pokemon Adventures by Kusaka and the one by Anakubo. I bet there are some Clefairy fans out there that wish the anime had followed the Anakubo model (which it almost did).
I'm more concerned about the in game mechanics over the movie. From the trailer for the game, I just saw it attacking, no transformation. (This is all speculation), considering how the player fought him in red and blue and fire red and leaf green, I expect to catch it the same way. I can't imagine there being a move that Mewtwo uses to transform, because it would always have to have it, their are only four move slots, and it could not have it replaced. So in short, I expect to find it and battle it in awakened form exclusively in the X and Y. Should the game involve some transformation in battle, then I would complete be good with that in Smash. Should the transformation occur as part of the story, I would prefer that it remains in awakened form if you battle and catch it in awakened form.
Medusa is much more classic to me. I remember reading about her in Nintendo Power back in the day. I could never get through KI as a kid at all, but she was so prominently remembered as the series villain. She and the eggplant wizard. I don't think Vridi is more likely since her ties to the original, but I can see Hades being more likely. She still figures very prominently in KI:U, so I don't think she's that much of a long shot. She is still the original final boss.
Hades would work better for me as a boss and a codec type of part for the KI stage.