Sen. John Ensign (Nev.), chairman of the Republican National Senatorial Committee, has a bold goal for 2008: 41 Republican seats. Out of 100.

Speaking with the press, the Republican leader has taken note of the noxious environment for his party and has set his bar for success at limbo levels: enough seats to prevent a filibuster-proof Senate. With Barack Obama favored to win the White House, and with Democrats almost assured of increasing their 37-seat U.S. House advantage in November, the Senate will be the last line of defense against the Obama-Democratic agenda. Every seat will be precious.

This much is sure — the GOP’s 49 seats in the Senate are almost certain to erode. Democrats will sweat their own seats only in Louisiana and possibly New Jersey. Republicans are virtually guaranteed to lose seats in Virginia and New Mexico, and face tough battles in no fewer than nine other states. While few Democrats will admit that 60 seats are within reach, the goal, unlikely as it seems, now appears attainable.

However, Democrats won’t need 60 seats to have a functional filibuster-proof majority on a host of important policies. In matters of healthcare, the economy, trade and even Iraq, there will be enough moderate Republicans and endangered 2010 colleagues to pick off on an issue-to-issue basis.

Progressive Punch, a service that tracks legislative votes, notes that in this Congress, Maine’s Olympia Snowe (R) has voted in opposition to her party 56.27 percent of the time — making her more loyal to Democrats than South Dakota Democrat Tim Johnson. Snowe’s Maine colleague, Susan Collins, has voted against her Republican Conference 48.98 percent of the time. Gordon Smith (R) of Oregon clocks in at 41.81 percent. Assuming Collins and Smith survive their tough election battles this year (no sure thing), Republicans won’t be able to always count on them for their 41-seat firewall.

Another two less-than-loyal Republicans — Pennsylvania’s Arlen Specter (47.79 percent) and Ohio’s George Voinovich (31.96 percent) — will be top Democratic targets in 2010, and will be looking to bolster their reelection bids by further distancing themselves from the tainted Republican brand. Can Voinovich realistically continue, for example, to vote against health insurance for low- and middle-class kids and still expect to win reelection?

After all, Ohio is a state that isn’t merely turning bluer by election, but sports one of the nation’s most re-energized and aggressive Democratic parties.

Up in New Hampshire, GOP party loyalist Judd Gregg will also be heavily targeted in 2010, in a state that cleaned house of Republicans in 2006. Missouri’s Kit Bond similarly must face voters in two years in a state that has suddenly lost its patience with corrupt and incompetent Republicans. The more they stick with their conference, the greater the chance they run of becoming the Rick Santorums of 2010 — too reactionary for their states, and fired by the voters as a result.

So let’s take a highly contentious bill, like the Employee Free Choice Act, which would allow card-check elections to unionize workplaces. Bitterly opposed by Republicans in this Congress, the measure failed cloture by 51-48. That vote included a Republican defector — Arlen Specter. No Democrats defected. The missing vote was that of Tim Johnson, out because of illness.

Can Democrats pick up the eight votes necessary to enact what would be the most significant pro-labor legislation in generations? Even if the voters don’t deliver that number, Democrats should be close enough that one or two desperate defectors from GOP ranks should be enough to pass this and just about any other bill.

Moulitsas is founder and publisher of Daily Kos .