Big no on Tom Cruise. I, unlike Shecky, dislike the crap out of Cruise. Never have liked him. He seems entirely insincere about anything and everything that comes out of his mouth. Barring that, he would actually make me distrust Michael, which is something that should NEVER happen.
Fillion as Michael, I can definitely see, although Shecky is right in that there would be massive potentially primo snark lost in translation here. I think I could be okay with it, though, as long as whoever plays Harry brings it for the both of them. He's played serious roles before (a misogynistic priest who was really an agent of the First Evil on Buffy, which was just flipping creepy; a doctor who falls for Keri Russel's character in the movie Waitress; and despite the completely BA snarkiness of the character, Captain Malcolm Reynolds was deeply serious, too.)
In the end, I'd still have to see a screen test to be sure. Michael is one of the best characters in the series (he's in my top three, right after Harry, Karrin and Thomas, and no, I didn't count wrong -- Karrin and Thomas share the number 2 spot). I love Nathan, but my top pick for Michael is still Viggo Mortenson (at least until something epic happens and they discover an unknown who completely kills the role).