Not to sound unoriginal, but yes, I want Ganon to be the villain of Zelda U, both in human and beast form. The last game we saw Ganon in (not counting ports and remakes) was Twilight Princess, already seven years ago. Assuming Zelda U is released in 2014 (which is probably too early), it'll be a whopping eight years. The previous longest time without a full appearance was seven years between A Link to the Past and Ocarina of Time (six if you go by international releases), and that was during the infamous Zelda drought. Ganon's a cool guy. He's intimidating. He's basically everything a Zelda villain needs.
Should they use Ganon, I have a few suggestions.
#1: Make him active in the plot. Don't make him a background influence that must be killed at the end or someone who just shows up once or twice to present an excuse for more dungeons. Make him kill. Make him destroy. Give Link a personal, visual reason to kill that man.
#2: Don't shoehorn beast Ganon in. The original beast Ganon was clearly intelligent and capable of speech. Let's see him use that stuff in the next encounter.
#3: Showcase his relationships with others. Is Ganon also the nemesis of another feared dark lord? How does he treat the oppressed townsfolk on a daily basis? Any (dare I say it) love interests? I want to see how this man operates, what he thinks and feels. The Wind Waker opened the door a creak. Zelda U is the perfect time to fling it wide.
#4: Reveal more of his past and ambitions. Again, The Wind Waker started to do this. Let's have Zelda U complete that process by showing us how the Gerudo viewed him or what rival thieves thought of him. Do we need some obligatory "Look, it's baby Ganondorf!" appearance? No, not necessarily, but I'd like to know more about who Link's supposed to be killing.
Assuming Ganon is not the main antagonist (and he very well may not be), I think Link should go up against a force, not just an evil person. Giygas from Earthbound is something of an example. Giygas used to be a person - now he's a nightmare-inducing force of evil. Perhaps Link could race against time to save the world from an otherworldly force of darkness. This would be something new and refreshing.