Byron York has written a good summary of the reasons why Santorum lost in 2006:

With all the other factors going against him, the personality factor helped sink Santorum in 2006. Yes, it was a bad year for Republicans, but Santorum’s 18-point loss was larger than any other GOP senator. It was more than just a defeat; it was a personal repudiation [bold mine-DL]. In private conversations with friends, Santorum is said to understand that he sometimes came on too strong for the voters’ comfort. It’s something Santorum still struggles with; he can still be argumentative, still be determined to win a dispute he probably shouldn’t be having in the first place.

So Santorum’s defeat was a complicated affair. He can blame a lot of different factors, but in the end he was most responsible for his own fate.

York discusses the Iraq war as a major factor in Santorum’s loss, and he gets this almost exactly right, but what York doesn’t touch on is that Santorum had simultaneously tied himself to Bush’s disastrous Iraq policy while also demanding more aggressive action elsewhere. Constantly talking about the great need to confront the Iranian-Venezuelan axis is bizarre and would be a hard sell at any time, but doing it in a year when sectarian violence was raging through Iraq and U.S. forces were taking significant casualties every month was madness.

In addition to being thoroughly rejected by his state’s electorate, Santorum has shown in the years since then that he has learned nothing from the experience. Instead of being chastened by a landslide defeat, he became even more certain that the aggressive foreign policy he had been preaching was right. I wouldn’t expect him to have tossed out all of his foreign policy views just because he lost, but one might think he would have gleaned something from the public’s repudiation of what he was offering them. Almost all Republicans in Congress supported the Iraq war at the beginning and still supported it in 2006, so it’s not as if that by itself was what dragged him down. What made the war a particular liability for Santorum was his dogged insistence that the Iraq war had been right and necessary when the overwhelming majority of Americans had realized that it had been a horrible mistake. Santorum’s greatest liability is not just that he favors a more aggressive foreign policy than the disastrous one Bush pursued in his first term, but that he is even more stubborn in defense of Bush’s bad policies than Bush was, and we could expect the same mindless “stay the course” approach from a President Santorum.

Update: Via Andrew, I see that Romney is recycling the lame, self-serving Republican argument that Santorum lost because of excessive spending. This was the standard excuse used to explain the 2006 loss of the House and the Senate while not mentioning the war, and it was usually expressed in the most ridiculous way (“too many earmarks!”). It didn’t matter that this excuse was completely untrue. It gave Republicans a way to think about the defeat without examining any of their serious mistakes. While it’s true that Santorum was fiscally irresponsible (especially on the prescription drug vote), that was not why he lost his bid for re-election.