Normally, a Senate incumbent has a strong advantage going into an election--but this year is not normal year. 2010 is one of the strongest anti-incumbent years decades, and thanks to a series of timely retirements, Republicans effectively have almost no incumbent senators facing tough re-elections.
In the states that were likely to be competitive anyway--New Hampshire, Ohio, Missouri, Kentucky, and Florida--the Republican senator is retiring. Only Richard Burr of North Carolina and possibly David Vitter of Louisiana are incumbent Republicans likely to face tough general elections.
The advantages to incumbency are normally huge--established name recognition, fundraising, years to build up support and rack up favors, etc. This year, however, it comes with a serious drawback--people very upset with Washington and record low feelings that current members of Congress deserve reelection. Individuals like Marco Rubio in Florida also show the desire to inject new blood into Washington provides a serious fundraising upside of its own in this environment.
While, in the end, Senate Republicans might have been slightly better off if they could have stopped a few of their own from retiring, they probably could not have chosen a better year to defend several open seats in what are normally considered swing states.