It could very well work as a spin-off game. I myself am really wanting a sidegame, "The Legend of Groose", that delves even more into his side of the story, whether that would be after the events of SS or during. And even in main titles, if every now and again a part of the game were to switch over to another character, like the Arbiter from Halo 2, that would also be a really fun idea, helps flesh out the world more.
But to leave Link out altogether in a mainline game... Idunno, I guess it COULD work, but I don't see why you would need to do that, considering Link is the main protagonist of the entire series. He's been established as such from the very beginning. Other things about the series have come along later and wouldn't be so bad messing with, but this one seems a bit more set in stone. I'm a fan of fleshing out the world and making it more believable, but I don't think you need to take out such a key component in order to do so. I'm not saying the game would turn out bad just because of it, I'm sure that if they really worked at it it could turn out to be a great game that no one saw coming like what happened with MM, but it just seems unnecessary to me. The games already change a lot from entry to entry, it's good to have at least SOMETHING in common to connect the disparate games together, like... idunno, a tether or a link or something...