I agree with a lot of what has been said so far. A lot of people who lost in 2010 OTL will not lose in TTL, and some of them may make presidential runs, however I think the Democratic nomination is Hillary's to lose, more so in TTL than 2016 OTL. As others have said, there is not record as Secretary of State to defend and if Obama loses (narrowly I can't see McCain doing better than Bush in 2004) there's going to be a lot in the party arguing "If only she won the nomination in '08, she'd have beaten McCain." So unless she sits it out, or messes up royally, she's the nominee.
As for the general, she wins and does so in a landslide, especially if McCain sits the 2012 election out. McCain would handle the economy worse than Obama did OTL as domestic policy and economics were never McCain's strong points, and internationally, we wouldn't withdrawal from Iraq, Afghanistan has a bigger surge, and we possibly have a third war in Syria, Iran, or Libya, heck we may even have four. As someone who supported McCain until he picked Palin and the economy collapsed, I'm DAMN glad Obama won in hindsight.