Personally, I think Dr. Mario, Pichu, and Roy(
) are gone for sure.
Young Link might be given his own moveset and/or have his graphical style redone into Wind Waker/Phantom Hourglass Link.
Ganondorf will definitely return due to importance, though his moveset will most likely be redone completely.
Despite Lucas, I can't see them cutting out a character like Ness. I think Ness and Lucas will be semi-clones.
Jigglypuff, Luigi, and Captain Falcon will return, without a doubt.
Mewtwo has a high chance of returning, though I hope they improve his moveset.
Marth also has a high chance of returning since he's the original Fire Emblem hero and he has a new game coming out.
I'm not sure what to think about Mr. Game & Watch. He may return due to being Nintendo's first video game character.
Sheik is a toughy. She may not come back due to Zelda being in her Twilight Princess design, but then again, her Ocarina of Time outfit is also selectable. Sheik might be given a new original design to blend more with the new Zelda, or who knows, Sheik might be an entirely separate character.