Mewtwo as a boss would be disappointing. The "bosses" in Smash Run look to be more like mini-bosses anyway, or some kind of events during the play. They seem to be more minor characters in their respective franchises, but still big/known/iconic enough to count as mini-bosses. There's Bonkers from Kirby and apparently Bulborb from Pikmin is one (?) too, and if we believe the Gamexplain video, (Mini-)Kraid and a big Kremling as well. So I'm thinking Mewtwo would be too big of a name to be shoved into that category haha!
That said, another legendary as a boss could work, though I think many, if not all of them, will be saved for Master Balls. So a boss in Smash Run could be something between a normal Pokémon and a legendary Pokémon => pseudo-legendary. Hydreigon, for example, as a mini-boss-sort-of-thing in Smash Run might work. But if there's actually going to be a Boss Mode of sorts, especially in the Wii U version, then I'd be fine with Rayquaza coming back, or Giratina or Yveltal being the boss or whatever.
As long as Mewtwo is playable haha!