I personally don't think she should accept this position. Chris Powers at Open Left thinks that it's a gamble, but one that could pay off.
"This is a high-risk, high-reward opportunity for Hillary Clinton. If she accepts, and serves out six or eight years in a popular Obama administration, then she is practically guaranteed the Presidency in 2016."
Powers also mentions that if Obama is unpopular or public opinion turns on her and she's replaced, then that would be the end of her public life. Her call. I think it would be wiser to stay out of the limelight for a few years and work on getting some solid health care reform under her belt. Both Kerry and Richardson are receiving some attention as well and I am not a fan of either one of them being in the top position. Kerry has no chance in my opinion. Obama would not look like the "Team of Rivals" man that he once claimed to be and Richardson just doesn't sit well with me either. The SoS job is one where you don't want a rival at the helms, but Kerry would rile up the right too much and they don't deserve any more attention for at least a decade.
Wes Clark would be the best choice, but my dreams have been dashed too many times to get worked up about this.