The frontrunners for the position appear to be either CIA Director Leon Panetta, or even General David Petraeus (scuttlebutt says that Petraeus could be appointed CIA Director if Panetta moves to the Pentagon). The reasons behind this are Panetta's loyalty to the President, his tendency to stay in the shadows, and the fact that it would give General Petraeus a high level position through 2012 that is not the presidency.
These seem to be bad reasons. Firstly, the idea of loyalty is somewhat overblown in the current political climate. Secretary Gates, as we all know, was originally appointed Secretary of Defense by George W. Bush and continued to hold this position under Obama. It's not as if the only way for Obama to guarantee loyalty in his SecDef is to appoint someone to the position that he has already appointed (Panetta was appointed by Obama in 2009 to head the CIA). Secondly, Panetta's low profile, while certainly not a negative by any means, wouldn't exactly be a reason for Obama to appoint him as SecDef. Obama's first Cabinet, known by some as the "Team of Rivals," includes people such as Hillary Clinton, who isn't exactly a low-profile name (and was also Obama's main rival during the 2008 primary). Thirdly, the fears of "Petraeus 2012" are overblown. Almost no one gives any credibility to the idea that he would run in the next election.
If not some combination of Panetta and Petraeus, then who should be the next SecDef? As you might guess from the title and the picture, I think Colin Powell would be a wise choice. In Powell, you have a person who is familiar with the structure of the military (retired four-star), certainly more so than Panetta. Politically, Obama would be replacing a Republican SecDef with another Republican SecDef, a consideration that can't be overlooked. Powell would also get a chance to be one of, if not the key figure in the Cabinet going forward (especially with Secretary Clinton on the way out), which is a chance he did not get in his role as Secretary of State.
The fact that he is intimately familiar with the State Department is another plus for his appointment. Gates is known to have been allied with Secretary Clinton on many issues. This warm relationship between Defense and State is crucial to the types of wars that the U.S. is currently facing, and the relationship needs to continue. And if this all means a return to the Powell Doctrine, then that's just a bonus.