Taking inspiration from commenter Art Deco in this thread, I think it is helpful draw distinctions between Republican candidates who are more liberal than most Republicans and liberals candidates who happen to be Republicans. The second category is, at the congressional level, pretty small at the moment. Lincoln Chafee comes to mind as the most recent example. I'm generally in favor of running primary challenges against such liberal Republicans even if it throws the election to a liberal Democrat. The main effect of such principled liberal Republicans is to give bipartisan cover to liberal initiatives.
The first group (to include Specter, Crist, the Maine Senators) is more complicated. They usually don't have liberal (or conservative) principles. They are running as Republicans in marginal or liberal-leaning constituencies (or maybe even right-leaning constituencies) for complicated and self-interested reasons. Since they are all about themselves, they tend to take losing very badly. They have to maneuver against powerful crosscurrents. Their branding as "moderate" or "independent" Republicans (which consists of voting with the Democrats when they perceive public opinion in favor of a given liberal position) means they will be to the left of the Republican Party. Their need to win primaries among right-skewing Republican primary electorates means they will vote well to the right of liberal (and most "moderate") Democrats. It isn't for nothing that all the moderate Senate Democrats voted for Obamacare and all the moderate Senate Republicans against. I would obviously prefer a conservative to a moderate (or just plain hack) Republican whenever possible. I'm glad we will (hopefully!) have Senators Rubio and Toomey rather than Senators Specter and Crist. But it isn't clear that a trading a moderate Republican for a liberal Democrat is an upgrade.
That doesn't mean we are stuck with the moderate Republicans we have. I think it is possible to get a Republican substantially to the right of Snowe and Collins elected to the Senate from Maine. I don't just mean knocking Snowe or Collins off in the primary, I'm talking winning the general too. It would take the right candidate, a populist message, a prudent, measured, and relevant issue agenda, alot of money and a favorable environment, But that doesn't mean that nominating a badly flawed conservative no hoper (or very little hoper) and giving the Senate Democrats one more consistently liberal vote makes for a better Senate.