Several factors. First, 2006 was a bad year for pubbies in general. Second, the MSM launched a full broadside of attacks against him - some of which have been shamelessly and uncritically re-used by his opponents on FR. And third, the Dems finally ran an ostensible pro-lifer against Santorum - Bob Casey Jr. might be weak-chinned, but his father was about the last great pro-life Dem, and pro-life Dems remembered the name. Throw all of those together and the deck was stacked against Santorum in 2006.
Bob Casey Jr has now shown he is not pro-life