Rubio should worry more about being re-elected to the Senate first. Then again, that's part of the reason Edwards ran in '04; it was likely he would be defeated in NC.
I don't think Rubio cares about his Senate seat as such. Like Obama, the point of running for Senate was to set himself up for a presidential run.
The only reason I'm not putting him in the top category of most likely to run here:
https://uselectionatlas.org/FORUM/index.php?topic=168823.msg3611987#msg3611987is because there is a small chance that Bush decides to run and blocks Rubio. But like I said above, I don't think that's all that likely.