I'm sure it worked well for Sonic X having non human characters (even though the majority of them were in fact humans, but it wasn't originally going to be that way).
But yeah, the manga would be the catalyst for the anime, just like for Dragonball, One Piece, Naruto, and other anime-adapted mangas. This manga (and anime) would basically be everything that FiM isn't, and what bronies want it to be, while still much of it being slice of life. Instead of having a "mane 6", there'd be a larger cast of main characters (both mares AND stallions, as well as some love interests.
While the manga/anime series would be mostly slice-of-life/comedy/romance/adventure-ish, the movie serious would be more epic in scale, having more action packed, darker, and sadder moments, but still have some humor involved.
OVAs would mostly be random adventures, not up to the scale of the film series, but would have a slightly bigger scope than the TV series. Same for the animation quality, not as elaborate as the movies, but better looking than the TV show.
Specials would mostly be side stories