Yeah, I think her only real chance to win the nomination would be to totally rip apart the Obama administration saying, "I left because I could no longer be party to the gross mismanagement there and the impact it's had on the DNC." Doing that would alienate a LOT of people and, even if she got the nomination she'd get destroyed in the general election because she'd still be tainted.
I think when she took the Sec State post, she knew she only had two chances of ever getting elected:
1) The Obama fares so poorly that he doesn't seek (or only vaguely seeks) the nomination in 2012. She gets it and steps in to save the party.
2) She waits patiently until 2016, lining up favors, and building a mass money-making machine.
The only way I could see her having a chance is her not excepting the Secretary of State post, then after the 2010 midterms say that given how disastrous the first two years of his term was, losing the House and a near filibuster proof majority in the Senate, how poorly his budget proposal was received (either 98 or 99 to zip IIRC) the difficulties he had with large majorities in both houses of congress in getting Health Care passed, etc. that unless there is a primary for the 2012 election (Usually the incumbent party doesn't run one.) then she would have no choice but to run as a third party candidate for the 2012 election. Even then I doubt she'd beat him. She's obnoxious and disliked.
Plus the establishment wing of the party would be more against her in 2012 than in 2008.