When a very conservative Republican Senator from Utah (Utah!) is at risk, we know the Republican Party is in deep, deep trouble. It does seem to be the case that the party rules in Utah are particularly problematic for an incumbent in a year of anti-incumbent anger.
It may be the case that both parties are in deep trouble, as incumbents from both are likely to face some significant challenges. The Democrats, as the party in majority, simply have more seats to lose, and, because of past success (thanks lil Steve for that), they have more fragile seats.
Still, it is more likely that the primary processes of the Republicans will go awry with some serious outbidding to the right. Then the question will become--will the damaged Republican or his/her entirely too far to the right/loony direction (one can move to a loony, non-right direction, to be clear) replacement be competitive against the Democrat so that the increased turnout among the anti-incumbents overcomes the revulsion by the mainstream? That is, does the median voter, due to motivated turnout by Tea Party and other folks, move either far right or simply off the scale? Or do these folks just pull the Republican candidate so far away from the middle that the turnout of "populists" is offset by the Dems, the independents and the Republicans that we used to think of us being only mildly conservative?
Interesting times indeed.