The guessing game about President Barack Obama’s second-term cabinet has already started, and one of the biggest questions is who will replace Secretary of State Hillary Clinton, and how that will affect U.S. foreign policy.

Clinton has announced she plans to leave shortly after Obama’s inauguration in January, to take a much-needed rest from her grueling traveling schedule in recent years. Among her likely successors:

• Sen. John Kerry, chairman of the Senate Foreign Relations Committee and Obama’s prep partner for the recent presidential debates, is the most widely mentioned candidate for the job. A patrician-looking Massachusetts legislator, Kerry not only has the advantage of a certain celebrity status — he was the Democratic Party’s 2004 presidential candidate — but would be easily confirmed by the Senate, where he has been serving since 1985.

Kerry’s biggest problem: if he leaves the Senate, a special election will be required to fill his seat, and the White House may fear that Republican Scott Brown — who lost his Senate seat Tuesday — could win it. That could put at risk the Democrats’ thin majority in the Senate.

• Amb. Susan Rice, current U.S. Ambassador to the United Nations, is one of Obama’s most trusted aides. Her passionate defense of Obama’s policies, especially on African issues, make her Obama’s preferred choice for State, some officials say.

Her problem: After the Sept. 11 attack on the U.S. consulate in Benghazi, Libya, Rice was widely criticized by Republicans over her statements suggesting that the incident was a spontaneous protest, rather than a terrorist attack. Rice could face a hard time being confirmed by the Senate.

• Tom Donilon, Obama’s current national security adviser. A Washington lawyer and former Clinton administration State Department official, he was appointed to his current job in 2010. His problem: Donilon was a registered lobbyist for the disgraced Fannie Mae federal mortgage company until 2005, and would also face a tough Senate confirmation.

• Other candidates for the job are Deputy Secretary of State William Burns, former Republican senator Chuck Hagel, and former Ambassador to China and 2012 Republican presidential hopeful Jon Huntsman.

Asked whether there would be any changes in U.S. policy toward Latin America with any of Clinton’s possible successors, most Washington insiders doubt it. None of the likely choices has a background in Latin American affairs. (Clinton didn’t either, for that matter, except for her close ties with the Dominican Republic and Haiti, which she has been visiting for decades.)

Among the few areas in which there could be changes in Washington’s policies toward the region are the war on drugs, Cuba, and trade relations.

The Nov. 6 passage of pro-marijuana legalization amendments in Colorado and Washington state will put pressure on the Obama administration to accept starting formal talks with Latin American countries that want to either legalize some drugs or seek other alternatives to the war on drugs.

On Cuba, the fact that a surprisingly large 47 percent of mostly conservative Cuban American voters in Florida voted for Obama on Nov. 6 may encourage the White House to further relax travel and licensing restrictions to Cuba. Lifting the entire U.S. embargo is unlikely, however, because that decision would have to be made by Congress.

“The United States is not going to react unilaterally, but the vote in Florida strengthens the administration’s effort to open up a whole range of different engagements with Cuba,” says Arturo Valenzuela, former head of the State Department’s Western Hemisphere office.

My opinion: We may see some changes on drug policy and Cuba, but they won’t be dramatic. Washington will not support drug legalization, and — at least until Fidel Castro dies — Congress will not lift the most important trade sanctions on Cuba.

But there may be some changes in the trade arena, as the Obama administration steps up its effort to create a Trans Pacific Partnership (TPP) that would create the world’s biggest economic bloc. The Obama plan is focused on Asia, but would include some Pacific rim Latin American countries, such as Mexico, Peru and Chile.

The way many in Washington see it — they will never admit publicly — there are already two Latin Americas: one made up of mostly free trade, market-oriented Pacific Rim countries, and another made up mostly of commodity-based, populist countries on the Atlantic coast.

It’s not too difficult to foresee which of the two Latin Americas the Obama administration will seek to forge closer ties with. Washington’s full-scale focus on the Pacific rim started under Hillary, and will intensify by whomever succeeds her.