I don't see Paul Ryan getting the nomination, and I think Rubio is aiming for President. However, he will likely have to run against Hillary, which would be a very tough race for him to win.
Hillary will be tough to beat especially if the economy is in an upswing and the wars are at an end. If Obama can tie up his 2 terms with a nice bow and hand the baton over, she'll be very difficult. What do you think of Michelle Obama's future? You think she'll pursue office? [edit] I think a Hillary/Michelle ticket would make cliffelam spontaneously combust.
She is, at the moment, maintaining she won't run. Realistically, I'm sure she will, because if she didn't the Democratic Party would be left in the cold in 2016. If Rubio ran against Hillary, she would have the easiest time in the world painting him as inexperienced -- and she'd be right.