"There are going to be stark choices between a liberal Democrat and a conservative Republican," McCain says at nearly every turn as he seeks to portray Obama as out of step with the nation. The more the GOP nominee-in-waiting can frame the debate along those lines, and capture a larger chunk of the electorate's center, the better his chance to eke out a victory in an extraordinarily challenging political environment.
Of course, a slew of other factors will come into play, including experience, character and outside events.
And, although Republicans shy away from publicly discussing it, race could have an enormous role. Public attitudes about issues like taxes and health care have been tested for years, but no one knows whether the nation will elect a black man, Obama, as president.
Age is another unknown. McCain will be 72 in August and would be the country's oldest elected president; Obama is more than two decades younger.
Seeking an early edge, McCain has spent the past few weeks laying out arguments against Obama, who is on the verge of clinching the Democratic nomination over. McCain has claimed that Obama lacks experience, raised questions about his judgment and suggested that the Democrat offers change that could imperil the country.
At the same time, the Vietnam prisoner of war and four-term senator has started trying to make the case that he alone has the qualifications to be a wartime commander in chief, in effect using his experience to counter concerns about his age.
Six months out, polling shows McCain competitive against Obama, and that heartens McCain's advisers, who recognize the difficult landscape for a Republican after President Bush's eight-year tenure.
In a sign of the troublesome times, the GOP has lost three special elections to fill vacant Republican seats this year.
The backdrop to those defeats: Bush's popularity is low, and a vast majority the public doesn't like the direction the country is heading. It's on the brink of a recession - if not already in one - and it's in the sixth year of a costly Iraq war that most people no longer support but that McCain does. Fundraising figures and primary turnout numbers also indicate that the GOP base isn't nearly as revved up as its counterpart.
Conversely, Democrats have a public hunger for change on their side. They also are on the cusp of nominating a fresh-faced candidate who has raised more than $200 million in more than a year, can pull in 35,000-strong crowds, and who long has opposed the Iraq war. The Democratic Party also has registered untold millions of new voters in key states.
Despite all that, Republicans say that if anyone gives them an opportunity to overcome the hurdles, it's McCain. They argue that he's not a typical GOP candidate and claim he has a necessary broad appeal for the times. They say his reputation for bucking the GOP on salient issues like climate change allows him to reach beyond the traditional Republican base when the party's "brand" is broken to attract independents and moderate Democrats.
"Both candidates will represent change. The question will be the right type of change versus the wrong kind of change," said Steve Schmidt, a senior strategist for McCain. "Senator Obama's inexperience, his lack of judgment, his naïveté, his lack of accomplishment will all be part of the debate."
So will ideology.
"There is an overwhelming difference between the right-of-center John McCain and the most liberal member of the Senate, Barack Obama," said Frank Donatelli, the Republican National Committee's deputy chairman. "The contrast is great on the issues."
Indeed, the GOP already is portraying the Democrat - who honed his political skills in Chicago after attending Harvard University - as a big-government advocate who wants to raise capital-gains taxes and recklessly pull U.S. troops out of Iraq and is willing to meet with leaders of U.S. enemy nations.
"By all yardsticks, this man is a legitimate leftist candidate," said Ron Kaufman, a veteran GOP strategist. "The good news is you don't have to paint him as that. You just need a mirror."
Dismissing the criticism, Obama spokesman Bill Burton said: "This is less about left and right. It's about which candidate is going to take this country in a new direction."
Democrats claim McCain is not that candidate, and they argue that he offers nothing more than a continuation of eight years of Bush's "failed" policies on Iraq and the economy.
McCain, in response, points to his record of challenging the party line on those and other issues.
Mindful that the unpopular Bush is a liability, McCain has started to distance himself from the president in speeches that encapsulate his own vision. Still, McCain is signaling he will use Bush where necessary; the two, for example, are appearing at a joint fundraiser later this month.
McCain is taking a campaign approach unlike Bush's elections in 2000 and 2004, which emphasized turning out the party's base. Rather, McCain has started shifting to the electorate's center, a recognition of his ideological reach as well as the need to capture swing voters against an opponent who also attracts independents.
He hopes his crusade against climate change - an issue that appeals to people of all stripes - will help him build a winning coalition of voters.
To do so, McCain is targeting traditional swing voting groups, like independents and Catholics, as well as others where Obama has shown weakness in the primaries, among them conservative-leaning so-called Reagan Democrats, blue-collar whites, Jews and Hispanics.
Because of McCain's independent streak and Obama's vulnerabilities with key demographics, Republicans see opportunity in several states Democrats won in 2004, including electoral-rich bastions of Minnesota, Wisconsin, Pennsylvania and Michigan.
There and elsewhere, race is surely going to be a factor, even though the GOP says it doesn't want it to be.
Said Donatelli: "We're all Americans, too, even though we want to win, and it just would not be in anyone's interest for race to become a part of this campaign." McCain himself acknowledged last month that benefiting from latent prejudice in the country "would bother me a great deal."
That's not to say groups operating independently of McCain's campaign won't wade into the black-vs.-white area - or other areas.
Republicans, for instance, are giddy about Obama's recent rough patch that exposed hotspots.
They cite his comment that small-town people are bitter and, thus, cling to guns and religion, as well as the flap over whether he wears a flag lapel pin, and his relationships with former pastor Jeremiah Wright and a 1960s-era radical William Ayers.
"There are some gifts out there that the party's been given," said John Truscott, a GOP strategist in Michigan. "The party has to be careful not to go too far, but these are issues that are fair game."
Republicans can only hope the general public sees it that way.