The election of Messrs. Obama and Biden to the presidency and the v.p.'y and Mr. Obama's selection of Senators Clinton and Salazar to head the State and Interior departments might very well weaken the Democrats' hold on the Senate.
The Illinois seat, which might conceivably go to a Republican in the wake of Mr. Blagojevich's scandals. Even if a Democrat is named, he or she will have to face reelection in two years under the taint of corruption. Maybe if the General Assembly isntitutes an early election--effectively taking from the Governor the power to nominate the new senator--and a Democrat gets elected, that person may very well face a strong challenge come election time in 2010.
In the other seats, a Democrat will likely be named. However, it is a risky proposition whether the person so named will have the sort of constituency that will enable him or her to retain the seat. Such is possibly most likely in Colorado, where Mr. Salazar--a rather conservative Democrat--may be difficult to replace. I don't know enough about New York (Clinton) or Delaware (Biden), but it seems at least not at all implausible that the Democrats there might face certain challenges.
The first midterm election afte the inauguration of a new president can be either an affirmation or repudiation of that president's policies. At least, it can be read that way: cf. 2002 and 1994. Even beyond the first midterm, Congressional elections tend to run against the party in power. My point is that if Mr. Obama is as aggressive at pursuing his plans as he claimed he would be during the campaign--and if he actually tries to pursue those plans--he might very well need to weather a political reaction in the next two to six years (i.e., the Senate elections are staggered). And now, four senate seats are potentially up for grabs.