Think that'll hurt him in the primaries? Right now the GOP needs to pick up only one seat with the presidency to retake it. However, they have only one seat they have a very good chance at (Louisiana), and the odds there look 50/50 at best, and they'll almost certainly at least one seat elsewhere. (Out of MN, CO and NH). They probably have an outside chance in SD, but the sympathy factor has probably blown that chance away (especially when you take into account what Dakotan people are like, from someone who knows that first hand).
So if McCain's elected, Napolitano appoints his replacement, and the GOP loses another seat. This basically all but assures the Democrats hold the Senate. How much will this hurt in the primary?
Unless, of course, its a McCain-Lieberman ticket...
Or if Lieberman gets an appointment...
Or if Lieberman caucuses with the GOP...
Or if Biden is on the national Dem ticket and forgoes reelection...