Manchin, who has enjoyed solid approval ratings throughout his tenure as governor, won re-election in 2008 with nearly 70 percent of the vote and carried all 55 counties. Halfway through his second term, the state constitution bars Manchin from running again for governor in 2012.
"If you're looking for a Senate candidate, you look for someone with his profile: He's popular, he knows how to raise money, and he has the desire to do it," said Jennifer Duffy, senior editor of the Cook Political Report.
Potential Republican special election candidates include Rep. Shelley Moore Capito. Already running for a sixth U.S. House term, Capito would not rule out seeking Byrd's seat when she joined calls this week for a vote before 2012.