I only have circumstantial evidence at my disposal, so take what I have to say with a grain of salt, but Mewtwo's inclusion isn't very far fetched.
As MorbidAltruism stated, Mewtwo has been planned for every Smash game to date, but was cut due to either tech limitations (N64) or time restraints (Brawl). So Mewtwo would have been an N64 veteran. However, despite his low-tier status, Mewtwo was, and still is, one of the most popular characters in Melee and all of Smash Bros, despite only being in one game, and before then, only one movie.
Mewtwo has been given a lot of love recently, thanks to Pokemon X and Y. Mewtwo was one of two pokemon to get two mega evolutions, the other being the recently confirmed veteran, Charizard. Not Lucario, who was also confirmed, Mewtwo. Mewtwo was a poster child for mega evolutions, and Sakurai (praise be unto him) has made several notes to point out that Mega Evolutions are incredibly powerful in this game, as they "had player expectations to fulfill." Not to mention starring in yet another film, and playing a fairly substantial role in Origins, Mewtwo's popularity as a pokemon is rapidly increasing. Plus, to coincide with the release of OR/AS, if Mewtwo plays any kind of role whatsoever in the game, it'd make sense to include him to boost hype for the game, along with the other previously confirmed pokemon.
On top of all this, Sakurai (praise be unto him) has never demoted a previously playable character to a Pokemon/Assist Trophy/Stage Hazard. They either stay in the game, or are cut entirely, but keep their trophy in the game, as was evidenced with Mewtwo, Dr. Mario, Pichu, and Roy.
Now, does this mean he's for sure to return? No, again, this is all just circumstantial evidence. But the hype train that is SSB4 is doing a lot of things right, and going so far as to develop a Gamecube controller adapter for one game means they love their fans a lot, and are obviously listening. They know about the fan demand for Mewtwo, that's not a question. But right now, all we can do is sit and wait to see what happens at E3.