Still, the front-runner's campaign ran into some trouble Wednesday after a senior adviser compared Romney's policy positions to an "Etch A Sketch" toy, suggesting they could easily change to appeal to more moderate general election voters.
"I think you hit a reset button for the fall campaign. Everything changes," said the adviser, Eric Fehrnstrom, during an interview on CNN. "It's almost like an Etch A Sketch. You can kind of shake it up and restart all over again."
Asked to clarify the remark, Fehrnstrom didn't back way from the comment. He said only that the general election is "a different race, with different candidates, and the main issue now becomes" exclusively President Barack Obama.
The comment played into the caricature of the former Massachusetts governor as someone who readily changes his positions to accommodate political realities. Romney supported abortion rights, for example, when he ran for governor of Massachusetts. Now he says he opposes abortion.
Romney and his allies spent hundreds of thousands of dollars more than Rick Santorum and his backers in Illinois, and it showed in Tuesday's results: Romney trounced Santorum by 47 percent to 35 percent.
Campaign finance reports released Tuesday showed that big donors to a GOP political organization founded by political strategist Karl Rove have boosted their financial support for Romney in recent weeks.
For all that money, though, Romney's Illinois win was a victory without an electrified electorate: Turnout seemed likely to be among the lowest in decades: Officials in several election districts said turnout hovered around 20 percent.
"You could draw a bigger crowd at a Green Bay Packers rally in downtown Chicago than what Mr. Romney delivered to the polls," Democratic Sen. Dick Durbin of Illinois said on CBS' "This Morning."
Romney was the clear favorite among Illinois Republicans who were most concerned about picking someone who is capable of taking on Obama in the fall. Romney's wife, Ann, suggested this week that it was time for the party to coalesce behind him. And in an appeal to the centrist independents who will decide the general election, Romney pledged Tuesday to work with Democrats or "die trying."
"Tonight was a primary, but November is a general election. And we're going to face a defining decision as a people," Romney said during a victory speech. "We know what Barack Obama's vision is. We've been living it these last three years. My vision is very, very different."
Romney picked up at least 41 delegates in Illinois, according to initial results, adding to his delegate lead and making it that much harder for any of his rivals to deny him an opportunity to take on Obama in November.
For his part, Obama on Wednesday headed to Nevada, New Mexico and Oklahoma on a trip aimed at answering critics of his energy policies, sure to be a key issue in the fall campaign. His first stop was a plant in Nevada that uses solar panels to power homes, part of an effort to highlight his programs to expand renewable energy sources.
The president's GOP critics poked back at Obama before Air Force One even took off. Newt Gingrich issued a statement saying Obama was answering a real-world problem with a "solution that is totally disconnected from the practical realities of the world and has little chance of success." Crossroads GPS, the nonprofit arm of a Republican super PAC, launched an ad on TV stations in the areas on Obama's itinerary and on national cable channels faulting the president for "bad energy policies" that are driving up gasoline prices.
Romney was moving on to Maryland, but he opened Wednesday by tweeting a "Happy Anniversary" message to his wife, complete with a wedding photo from 1969. His campaign also released a web video in which Ann Romney recounts the details of their dating-to-marriage story.
Polls show Romney has the advantage heading toward Maryland's April 3 primary. But the South, where Louisiana votes Saturday, has proven less hospitable to Romney.
Santorum, who hopes to rebound in Louisiana, sounded like anything but a defeated contender Tuesday night as he spoke to supporters in Gettysburg, Pa. He said he had outpolled Romney in downstate Illinois and the areas "that conservatives and Republicans populate."
"We're very happy about that and we're happy about the delegates we're going to get, too," he said before invoking Illinois-born Republican icon Ronald Reagan, the actor turned president. "Saddle up, like Reagan did in the cowboy movies."
Gingrich issued only a written statement Tuesday. Texas Rep. Ron Paul has yet to win a state.
Romney triumphed in Illinois after benefiting from a crushing 7-1 advantage in the television advertising wars, and as his chief rival struggled to overcome self-imposed political wounds in the marathon race to pick an opponent to Obama.
Most recently, Santorum backpedaled after saying Monday that the economy wasn't the main issue of the campaign. "Occasionally you say some things where you wish you had a do-over," he said later.
Romney has 563 delegates in the overall count maintained by The Associated Press, out of 1,144 needed to win the nomination. Santorum has 263 delegates, Gingrich 135 and Paul 50.
After the Louisiana primary, a 10-day break follows before Washington, D.C., Maryland and Wisconsin hold primaries on April 3.
Santorum is not on the ballot in the nation's capital. Private polling shows Romney with the edge in Maryland, and the pro-Romney super PAC Restore Our Future is spending more than $450,000 on ads in the state.
Wisconsin shapes up as the next big test between Romney and Santorum. Republican politics there have been roiled recently by a controversy involving a recall battle against the governor and some GOP state senators who supported legislation that was bitterly opposed by labor unions.
Already, Restore Our Future has put down more than $2 million in television advertising across Wisconsin. Santorum has spent about $50,000 to answer.