An unusually personal spat between Senate Republicans and President Barack Obama over U.N. Ambassador Susan E. Rice broke into open view Wednesday, setting up what could be a protracted power struggle if Obama decides to nominate her for secretary of State.

Newly assertive after winning re-election, Obama said it was “outrageous” for GOP senators to attack Rice over the handling of the September attack on the U.S. consulate in Benghazi, Libya. The episode casts new uncertainty over the shape of Obama’s national security team going into his second term, only compounded by the unexpected resignation of David H. Petraeus from the CIA.

Obama was defiant after Sen. John McCain of Arizona, the top Republican on the Armed Services panel, vowed Wednesday to do “whatever’s necessary” to block a Rice nomination.

“When they go after the U.N. ambassador, apparently because they think she’s an easy target, then they’ve got a problem with me,” Obama said at his first press conference since the election. “If I think that she would be the best person to serve America in the capacity at the State Department, then I will nominate her.”

Obama’s remarks appeared to signal that, freed of the political freight of needing to court voters, he will take a firmer tone on national security issues in his second term. In some ways, that shift began during the campaign in the second debate with GOP candidate Mitt Romney, when Obama pushed back hard on Romney’s attacks on his handling of Libya.

Obama’s decision to stand up to congressional Republicans, at least rhetorically, could foreshadow a willingness to take to Congress the fight over issues such as defense spending levels, Iran sanctions and aid to Arab Spring countries.

An early sign of Obama’s resolve would be if he decides to nominate Rice to succeed Secretary of State Hillary Rodham Clinton, who has long made clear she plans to leave at the end of his first term. The White House will also likely need to find a replacement next year for Defense Secretary Leon E. Panetta, who is not expected to stay long in a second term. And it’s not clear if national security adviser Tom Donilon will stay on or if he’ll be tapped for another post.

Obama certainly would be setting up a fight by picking Rice over someone like Senate Foreign Relations Chairman John Kerry, D-Mass., who has also been getting some secretary-of- State buzz and would be less controversial on the Hill.

“We will do whatever’s necessary to block the nomination as far as Susan Rice is concerned,” McCain said at a press conference with GOP colleagues Lindsey Graham of South Carolina and Kelly Ayotte of New Hampshire.

The three Armed Services Committee members have been among the most vocal critics of the Obama administration’s handling of the Benghazi attack that killed U.S. Ambassador J. Christopher Stevens and three other Americans. And they consider Rice among those officials responsible for the administration’s confused response to the assault and explanation of its causes.

McCain, Graham and Ayotte lambasted Rice in particular as untrustworthy for her statements on national television five days after the attack. She had said that it appeared to be the result of a spontaneous uprising prompted by an anti-Muslim video.

Rice’s comments were based on the latest intelligence reports provided to members of the administration and Congress, but the three Republican lawmakers maintained that they conflicted with reality.

“How could she say, five days later, definitively, that there’s no evidence of a coordinated attack when there’s a ream of evidence?” Graham asked. Her assessment, he said, was “so disconnected from reality, I don’t trust her. And the reason I don’t trust her is I think she knew better, and if she didn’t know better, she shouldn’t be the voice of America.”

Obama retorted that if the senators wanted to attack someone over Benghazi, then “they should go after me.”

That prompted its own reply from McCain and Graham.

“Mr. President, don’t think for one minute I don’t hold you ultimately responsible for Benghazi,” Graham said. But he added, “Given what I know now, I have no intention of promoting anyone who is up to their eyeballs in the Benghazi debacle.”

For some Republicans, the opposition to Rice goes beyond the Benghazi incident, which has reaffirmed their belief that she is too political and too much of an Obama acolyte to be named America’s top diplomat.

“I’m not so sure she’s the strongest advocate,” Graham added. “I think she’s more of a political operative than she is anything else when it comes to Benghazi.”

Graham also criticized Rice’s performance at the United Nations, something Sen. James M. Inhofe of Oklahoma, who is expected to become the top Republican on the Armed Services panel, raised in his own statement Wednesday.

While at the United Nations, “Rice has been the Obama administration’s point person in pursuing liberal causes that threaten U.S. sovereignty,” he said. Like the White House, Senate Democrats were quick to back up Rice on Wednesday, accusing Republicans of blowing her comments on Benghazi out of proportion.

“If the president should nominate her, I don’t believe that should be any reason to stop her,” agreed Senate Majority Whip Richard J. Durbin, D-Ill. “Sure, ask the hard questions — where did you get that information and why did you say this? — but to disqualify her based on a ‘Meet the Press’ appearance,” Durbin said. “I mean, to me, it goes way too far.”

Niels Lesniewski contributed to this report.