I'd like to make a list of reasons why Mewtwo will be back. Please add to the list if you have a good point, make sure I notice it so I can update the list.
Points for Mewtwo's return
1. He's iconic, unique, a legendary PKMN and very popular
2. He is playable in Melee (secret character)
3. Many want him to return to Smash
4. He was suppose to be in Brawl+++
5. He was in the latest Pokémon movie
6. He would fit in Pokkén Tournament and that would be a good link to Smash
7. Mega evolution: he was the first to be revealed as a mega evolution, it would fit in with Lucario, and especially Charizard who also has two versions just as Mewtwo has.
8. He was in PKMN X/Y
9. There were 6 PKMN in Brawl and in Smash 4 there is currently 4 (5 counting Jigglypuff), and with the fact that this roster is the biggest yet, meaning there is more room for more PKMN. Not to mention the fact that PKMN is Nintendo's second biggest franchise.
10. Sakurai's coy comment when asking about Mewtwo: "We are thinking about it".
11. There are at least 2-5 more characters to be added that we don't know about in order for the character select screen to make sense.
12. The possibility of DLC characters
13. Sakurai is a troll, he probably wants us to think he's not in it so the surprise will be greater.
14. He's playable in Project M
15. Smash 4 has a lot of "clones", with the time to create these there surely would be time to bring Mewtwo in this time. Also the return of characters like Toon Link and Lucario points to the fact that less worthy characters are back as well as Mewtwo.
16. Simply... Dr. Mario
17. ?