One thing to consider are the vulnerable blue state GOP senators up to reelection. They may need a way to vote to confirm or vote to end the filibuster in order to not be branded an obstructionist at home.
Will this one issue blow up so big that it'll actually tip multiple Senate races though? I'm skeptical. Aside from Kirk in Illinois, are there any incumbent GOP Senators from states that are so overwhelmingly Democratic that the issue will cut strongly against them? I'm not convinced it'll be a giant loser in, say, Pennsylvania or Wisconsin. Maybe it will, but I'm not sure.