Jonathan Bernstein notes an interesting phenomenon from the past year. In three different elections (Alaska Senate, Colorado governor, and the NY-23 special House election), the winner of the Republican primary was undermined in the general election by a conservative candidate who had the backing of disgruntled Republicans. This is important for the reasons Jon mentions -- primaries were designed to give legitimacy and finality to party nominations. If the primary doesn't really settle anything, then parties are much more prone to splintering.
Do three cases constitute a trend? I'm willing to county Joe Lieberman's 2006 re-election campaign as another case along these lines. Maybe these are flukes -- the Lieberman race occurred when Democrats were unusually split on the Iraq War, and the recent Republican races occurred during a time of unusual Tea Party activity directed, sometimes, against the Republican establishment. But if this is an actual trend, party leaders have a lot to worry about.