See here:
http://www.nbc10.com/news/4205235/detail.html?rss=phi&psp=news
If he were to resign from office, Democratic Governor Ed Rendell would get to appoint a Democrat to the seat, probably either Barbara Hafer or Bob Casey Jr. I would guess that he'd appoint Hafer and let Casey crush Santorum on his own (its looking more and more likely).
That would be an incredible changeover, for us to win both seats in two years.