Although there are numerous leadership shake-up scenarios, most agree that the current No. 2, Minority Whip Jon Kyl (R-Ariz.), would be the lead candidate to replace him.
The way Republicans do things generally, thered have to be a very serious realignment for Jon Kyl not to take the slot, the leadership aide said.
Kyl has worked his way up through the ranks to amass a long, policy-heavy résumé and understanding of the Senate, its rules and its Members. While a staunch conservative, Kyl also has cut deals in recent years, particularly on dicey topics such as immigration reform.
He is the top contender for the position, said another Republican Senate aide.
Kyl might be the heir apparent, but other possible candidates could also emerge, such as Sen. Judd Gregg (R-N.H.), one of the Conferences respected policy wonks who upped his credibility earlier this month in negotiating a bipartisan economic rescue package.
But Gregg has shied away from elected leadership posts in the past, and many say he is likely to continue as a back-bencher who serves as one of the leaderships top counselors.
One Republican also noted that Gregg has made few forays outside of budget and spending-related issues. Gregg hasnt had to deal with the pressures of managing a Conference. ... I dont know how well that translates into a leadership position, the Republican said.
Other ambitious Senators could consider running, such as Conference Chairman Lamar Alexander (Tenn.), but most Republican insiders believe Alexander is more likely to run to succeed Kyl as Minority Whip or stay in his current job as the top messenger for the Conference.
Another likely candidate to replace Kyl would be Sen. John Thune (S.D.), now the Chief Deputy Minority Whip. Thune has hinted at running for leadership in the past but opted against it. Many Republicans believe he would strongly consider making a run if the top Whip post came open.
Whether Alexander would run for it as well remains unclear, but he has sought the post before. He ran for it in 2006 against then-Sen. Trent Lott (Miss.), losing by one vote.
The dominoes continue to fall from there. Alexanders job as Conference chairman if he were to choose to run for Whip would have broad appeal as well. Several up-and-comers such as Sens. Richard Burr (N.C.) and Johnny Isakson (Ga.) or Conference Vice Chairman John Cornyn (Texas) could be interested.
Cornyn has started running for chairman of the National Republican Senatorial Committee, however, and many believe he will still pursue that job regardless of McConnells fortunes, although at least one Republican speculated that if the partys ranks are seriously thinned on Election Day, Cornyns name could come up as a potential challenger for a higher slot in leadership.
Also considering running for the NRSC next cycle is Sen. Norm Coleman (Minn.), who might look at other options if more than one job is vacant.
That leaves the current NRSC chairman, Sen. John Ensign (Nev.) , who has mounted a bid to serve as the GOP Policy Committee chairman next year. If McConnell lost, most believe Ensign would stick to his plan, but he could also consider running for Conference chairman.
Sen Mary Landrieu, D-La., poses for a selfie with LSU football fans as she campaigns at tailgate parties on the Louisiana State University campus before the LSU-Mississippi State game on Saturday, Sept. 20, 2014. Buy photo here.