I think Jon's exactly right that the primary significance of the Specter switch is less that he gives the Democrats a consistent filibuster-proof majority than that his defection represents another data point--and a big one--in the decline of the GOP as a national party. I'd only make one additional, region-related observation.
If I'd been a Republican looking at the map after the 2008 election, I would have seen a lot of very troubling signs: A Northeast that seemed out of reach for cycles to come, a Northwest almost as problematic, and a Southwest whose demographics look to make it more of a stretch with every passing election. The one place I might've taken some solace was the Rust Belt. Yes, Obama won there, too, but he was carried by Bush fatigue and economic insecurity. Demographically, I would have thought, these are folks who could probably be brought back into the Republican fold.
Since then, of course, the GOP has become the party of Let the Auto Industry Die (except, of course, for the foreign manufacturers with plants in the South) and has suffered the defection of a high-profile, long-serving Rust Belt Senator on the grounds that the party has grown too "extreme." Time will tell, but this looks like one more region that, barring a complete Obama collapse, could cause real trouble for the GOP (some states more than others, obviously) for some time to come.