While this Karen Tumulty column about Hillary's 5 mistakes has made the rounds, there are a couple additional factors, largely beyond the former First Lady's control, that ended up being highly significant as well.
1. John Edwards -- Many, many years ago, when Edwards was still a 2008 candidate, I recall the puzzlement expressed by those political pundits who noted the seeming contrast between Edwards' rather liberal populist campaign and the largely white, more conservative slice of the demographic pie he was pulling in the early contests. Edwards' vote base didn't really seem connected to the candidate's message. Demographics seemed more important than policy.
And while Edwards didn't stay in the race long, he placed a narrow second place in Iowa, ahead of Clinton. The story of the night ended up being Obama's rather comfortably sized--but still only a plurality--margin of victory. Had Edwards not opted for the race--and from the night of the 2004 election it was obvious he would run again--it is fairly easy to see Hillary winning a large portion of Edwards' vote, given how the last several contests have turned out. The presence of another, viable White candidate in the race hurt Hillary at this early stage, possibly dividing the White demographic and giving another strong candidate, Obama, an opening he desperately needed.
2. Michigan/Florida -- While the focus on these states has tended to be that of how to seat their delegates given the fact that they broke the national Democratic party rules and held their contests too early, and the fact that as a result Obama was not even on the Michigan ballot, it is still and ironically the case that had these states stuck to the regular schedule they would have ended up playing a much more significant role while giving Clinton two large and relatively early, momentum-generating victories. Had this occured, Obama's victories on Super Tuesday would have no doubt been viewed differently, and the nature of the contest reshaped.