With polls showing President Obama leading the presidential race, he'll likely play it safe in Wednesday night's debate against Republican challenger Mitt Romney, like a winning football team running out the clock and trying to prevent its opponent from making any major plays.

When he's on his game, Obama is a cool, calm and confident debater. But during his presidency, he's also shown himself to be thin-skinned and prickly when forcefully challenged. If Romney is going to change the dynamic of the race in its closing weeks, he'll have to unsettle Obama by challenging him on the aspects of his record on which he's most vulnerable. Here are six possibilities:

Health care: The unpopularity of Obama's national health care law was a key factor in the Republican takeover of the House of Representatives in 2010 and still remains a potentially large target. Given that Romney signed a similar law as governor of Massachusetts, it will be difficult for him to attack Obama on the issue without drawing charges of hypocrisy. Thus, the best chance he has to hammer Obama on the issue is to weave critiques of the health care law into his answers on other issues.

Economy: Obama, with the help of Bill Clinton's speech to the Democratic National Convention last month, has had increased success convincing Americans that he handled the economy as well as could be expected given the conditions when he took office. To win the election, Romney must refocus attention on the fact that the economy is not only still very weak, but in much worse shape than Obama promised it would be if his policies were adopted. The health care law, set to be fully implemented in 2014, will add to the burdens being placed on businesses in an already weak economy.

Deficits: When it comes to making the case about deficits, Romney should keep it simple: Obama promised he would cut the $1.2 trillion deficit he inherited in half in his first term in office, and hasn't come even close. In fact, the fiscal-year 2012 deficit is on pace to exceed $1.2 trillion. A discussion of Obama's fiscal management is also one way of bringing up the health care law, which is projected to cost $1.7 trillion over a decade.

Taxes: Obama has had success arguing that he merely wants to raise taxes on the rich, while accusing Romney of wanting to raise them on the middle class. Romney will have to hammer home the fact that Obama's income tax increases will hit 940,000 small-business owners, according to the Joint Committee on Taxation. His health care law will also raise a litany of taxes by a total of $1 trillion over a decade, according to the Congressional Budget Office, several of which will hit lower income groups.

Energy: One of the ways that Americans feel economic pain is through rising gas and electricity costs. This is especially true of lower-income Americans, because they spend a higher portion of their earnings on energy. Romney could gain ground with working-class voters by explaining how Obama's policies have contributed to these rising costs, and how his policies could help bring them down.

Libya: Though this is technically supposed to be a domestic policy debate, Romney shouldn't waste the opportunity to challenge Obama on his handling of the attack on the U.S. consulate in Benghazi. He should press Obama on why his administration focused attention on a amateur anti-Muslim video in the face of evidence of a coordinated terrorist attack and why there wasn't more security at the consulate.