Two thoughts:
1) Early on in the Obama administration Biden was seen as instrumental in passing the legislative agenda through Congress thanks to decades-long relationships he had developed on Capitol Hill. If you leaven Biden in the Senate, then you're going to have to rely on VP Clinton to ensure the passage of an ambitious agenda. I foresee two problems with this approach. First, she doesn't have the same kind of wheeler-dealer relationships that Biden was able to use to grease the wheels of Congress, and second, if she disagrees with the agenda then she might not be inclined to push it very hard. And on Obama's signature issue IOTL, the PPACA, Hillary would get the credit if it still becomes law because the media will see her as the plan's biggest and most powerful advocate. (In other words, we'll still be hearing about Hillarycare rather than Obamacare, with dividends for Hillary rather than her boss.)
2) In 2016 Hillary is going to be tied to every single policy of Obama's administration. During the primaries this spring she embraced most of the Obama agenda, with a few exceptions. She was able to make exceptions because of her absence in his second term cabinet allowed her a degree of flexibility which she wouldn't have if she were still serving as his VP. TPP? She would own that; no way to weasel out of it when her boss is telling her that it has to pass. She'd own the administration's veto of the 9/11 Lawsuit bill, another move that would increase her unpopularity. Basically, she couldn't help but be trapped by Obama and his administration's positions on key issues, preventing her from being her own candidate which she really needed to do to get through the primaries this year.
In conclusion, I think that both of those points would be evident to either Obama or Clinton when the veep selection was being made. Those are pretty tremendous drawbacks for both of them, which I think precludes the option of her being selected. If she was, though, I think that Obama and Clinton are both worse off for her accepting the job.