Sen. Claire McCaskill (D-Mo.) speaks to constituents during a roundtable discussion on the campus of the University of Central Missouri in Warrensburg, Mo. (Julie Denesha/For The Washington Post)

As one of the U.S. Senate’s most endangered Democratic incumbents, Claire McCaskill knows she’s a top target of the new conservative super PACs that have radically reordered the political landscape in 2012.

Independent conservative groups have already spent more than $3 million on television and radio ads in Missouri hoping to pick up one of the four seats that Republicans need to take control of the Senate.

McCaskill’s response has been an unconventional and risky strategy: She’s targeting the super PACs right back.

Standard practice suggests that voters are rarely interested in arguments over campaign finances, particularly in the face of a tough economy and a political system awash in money on both sides. But McCaskill is betting she can turn the millions spent against her into an advantage, a sign of her political independence. She devoted her first campaign ad for reelection to the argument that out-of-state special interests are trying to knock her out of the Senate in November.

“You make one company mad by casting a principled vote, and they say, ‘Okay, we’ll just gin up $10 million of our corporate money and take her out anonymously,’ ” she said. “I think if people figure out that’s what’s going on, they’re going to be very turned off by it.”

The McCaskill campaign will provide a key national test of whether too much money can be a disadvantage in a political campaign in 2012, particularly when McCaskill herself will be the beneficiary of some of the same kind of outside spending she criticizes.

“Time will tell,” she said.

Republicans note the outside spending might only level the financial playing field. McCaskill just announced that she has $6.3 million in the bank for the race, dramatically outpacing the fundraising of all three of Republicans competing to replace her.

And each of the GOP candidates — Rep. Todd Akin of St. Louis, wealthy former businessman John Brunner and former state treasurer Sarah Steelman — said that the issue matters little to voters and that McCaskill’s emphasis on it only proves she’s out of touch.

But McCaskill is betting that the political landscape has shifted since the 2010 Citizens United decision that lifted restrictions on corporate and union giving — and that she can use the relentless attacks to reinforce her message that she is an independent thinker who has made powerful enemies during her first term in office.

Missouri’s shift

McCaskill won election in 2006 by less than 3 percentage points in a race that now feels like an artifact of a different era, dominated by her opposition to the Iraq war and her support for an ultimately successful state referendum measure to fund stem cell research.

The state has swung decidedly rightward since Sen. John McCain (R-Ariz.) beat Barack Obama by just two-tenths of a percentage point here in 2008.

While Obama’s approval rating in Missouri lagged behind his national average by just one point in 2009, by last year it had dipped to 39 percent, five points behind the national average, according to Gallup.

For that reason, Obama could largely cede Missouri to the Republican nominee and focus on swing states where his prospects are brighter, leaving McCaskill alone to fend off the Republican offensive.

“She introduced Obama to the state of Missouri, and people don’t like that,” said Akin, who has represented the Republican suburbs of St. Louis since 2001.

An early Obama endorser, McCaskill now faces a geographic conundrum. To win, she will need to run up the vote in the Democratic strongholds of Kansas City and St. Louis, where ties to Obama could be an advantage. But she cannot lose too badly in the rest of the rural state, where he is more likely to be a drag.

In 2006, McCaskill was able to lean on her time as a youth growing up in small-town Missouri to close the Republican margin in rural areas. Her performance there was the difference between her Senate win and her close loss in a race for governor two years earlier.

But Republicans say that her charm has worn thin outside Missouri’s big cities and that the strategy will be difficult to repeat.

Her solution so far has been to try to build credentials as an independent thinker and tireless worker. She lost 50 pounds in preparation for the reelection campaign, a physical reminder of her focus and grit that even some of her opponents concede.

As signs of her autonomy, she points to her efforts to get rid of congressional earmarks, her oversight of defense-contracting abuse in Iraq and Afghanistan and her co-sponsorship with Republican Sen. Bob Corker (Tenn.) of a 2010 bill to impose spending caps on the federal government that failed amid Democratic opposition. The attack on super PACs is part of that narrative.

“If the president were to come to Missouri — as I’ve asked him to do — he’d be the first one to tell Missourians that I can be a real pain,” she said.

Each of her Republican opponents says McCaskill has aligned herself too closely with major Democratic priorities to make the argument stick. She voted for the stimulus package, backed the bipartisan compromise to raise the nation’s debt ceiling and, notably, voted for the 2010 federal health-care overhaul, which is particularly unpopular in Missouri.

“McCaskill is still trying to convince people of how great this health-care bill is going to be for them. And people in Missouri don’t like it. They don’t want it,” said Steelman, who built a reputation as a feisty conservative crusader as state treasurer from 2005 to 2009.

McCaskill’s best advantage might be the split Republican field.

Several high-profile Republicans declined to enter the race, leaving her with three lesser-known opponents who could bloody one another in a primary race that will last far longer than the quick three-month general-election race that will come after.

That race has so far been relatively genteel, with the candidates working to separate themselves largely on issues of résuméand personality. Only Brunner, who has promised to devote his considerable personal wealth to the campaign, has run television ads, and they target McCaskill, not his GOP opponents.

“The candidates have been very polite,” said George Connor, a professor of political science at Missouri State University. “It hasn’t gotten to the level of ugly — but there’s a potential for it.”

Mystery mission

At the end of a long day of campaigning this month, McCaskill was sitting in the back seat of a town car parked next to a Shell station in Kansas City when she noticed a young man approaching.

He had been quietly trailing her all day, whispering to a cameraman at his side as she toured a small-town factory, lurking in the back of the conference room when she met with business leaders at a local college.

Now he was headed toward her parked car, and she was worried. Among the first things that came to mind was all the super-PAC money being spent to defeat her and whether he was part of that.

“Does he want something?” she asked her driver, cracking her window open as the man approached.

“I don’t know who you are, but thank you for being here!” she trilled.

He said he worked for “GMMB” and he had just wanted to thank her for the day. Then he wandered off, his mission still a mystery.

It turned out the man was more likely friend than foe. GMMB is an ad agency that is generally hired by Democratic-leaning groups. But this is the new world super PACs have wrought: a stranger with a camera crew, shooting footage for an unseen boss to be used at an undefined time for an unknown purpose.

“It’s like shadowboxing,” McCaskill said, seated in the back of the car, heels off, massaging her bare feet. “You don’t know who it is that’s after you, why they’re after you. And you’ll never know.”

Polling analyst Scott Clement in Washington contributed to this report.