Nate Silver doesn’t think Secretary of State makes sense for Clinton:
If Hillary Clinton’s goal is to become President of the United States in 2016, would she improve her odds by accepting the Secretary of State position?
My answer to this is a qualified ‘no’. If the Obama administration is perceived as successful, that will likely make Clinton’s road to the White House easier. But this is probably true whether or not she serves in Obama’s Cabinet.
If the Democratic brand is strong in 2016, Clinton will have little trouble riding that wave and presenting herself as a safe, trusted, capital-D Democrat (which is essentially her brand to begin with), almost no matter what she had spent her time doing.
On the other hand, it would probably be easier for Clinton to extricate herself from an unpopular Obama had she avoided serving in his Cabinet. This is particularly the case if Obama loses in 2012, in which case Democrats would inevitably want to go in a "new" direction in 2016. Clinton would find it easier to present herself as that alternative if, say, she served as Governor of New York, rather than as a member of Obama’s cabinet.
The Dish 