Sean Hannity today made the case that she's dead woman walking. Politico makes the case that replacing her would be too problematic for team Obama to let her go. The Politico piece is probably right that Republicans would put Obamacare on trial with confirmation hearings for Sebelius' replacement.
I think the question is a green banana. If the ACA train wreck gets worse, it's hard to imagine President Obama not throwing someone overboard and the most obvious someone is Sebelius. He'll likely resist replacing her until the damage becomes so serious he feels he has no choice. But certainly the spectacle of Republicans grilling her would-be successor isn't something Obama will subject his administration to until he's convinced he's out of options. Even if they ultimately approve Obama's choice, Republicans will use the opportunity to lay bare what a disaster it is and sacking Sebelius would be proof that even Obama sees it that way.
If I had to guess, I'd guess she's staying. But that guess comes with not knowing how bad Obamageddon will get. And if Democrats start joining the chorus to fire her, fugget about it.