I think he will run, but I think if he really is gunning for the VP spot, he should stay in the Senate, endorse the eventual frontrunner fairly early, raise a lot money for him, and do well stumping for him. I think it'll become increasingly more likely that nominees won't pick people who ran against them in the primary, given how acrimonious and heated they've become. Can you imagine the things Marco Rubio, or any candidate for that matter, will have to say about the eventual nominee?
I don't see any reason to think that Rubio will be ruled out of running mate contention by running (unsuccessfully) for president. He should run for president John Edwards 2004 style, and stay mostly positive, without making viscious attacks on the frontrunners. Hope that, as with Edwards in '04, his campaign trail performance in the primaries makes him a stronger contender for the vice presidency.
He can't really run for reelection for Senate and vice president at the same time. Florida law won't allow it. If he's picked as VP, then sure, he could just drop out of his Senate race, but the party will have to scramble for a replacement for him. Better for him to just renounce reelection plans right now, and declare for president, in the hopes that if he doesn't win the nomination and Walker (or whoever) does, Walker picks him as his running mate.
If the ticket then loses in November, Rubio will have at least set himself up for 2020, having prevented anyone else from using the VP slot on the ticket to gain their own national prominence. Again, just like John Edwards tried to do in 2008. Edwards, of course, was stymied by Clinton and Obama, but Rubio will just have to hope that there is no Republican equivalent of Clinton or Obama who emerges in 2020 to stop him.