Stanford has never beaten USC four times in a row. But after a 55-21 loss in 2009 and three consecutive defeats at the hands of their Bay Area rivals, the No. 2 Trojans would make dubious history with a loss this weekend.

Grudge match · Sophomore linebacker Dion Bailey leads a unit determined to put an end to USC’s three-game losing streak to Stanford. Bailey had two interceptions in last week’s victory 42-29 over Syracuse. – Carlo Acenas | Daily Trojan

Given recent contests and the budding rivalry between the two, it’s a reasonable question as to whether Pac-12 opener is weighted with any additional significance for the Trojans. On the surface, USC (2-0) isn’t straying from its “prep, not hype” motto in advance of the highly anticipated showdown at Stanford Stadium.

“Every season’s new,” USC coach Lane Kiffin said. “Every year is different. They have a lot of new people. We have new people. It goes back to preparing really well and getting ready to go on the road in our conference opener.”

Despite this rhetoric, many players admit that winning this game would be more satisfying than an ordinary victory, as the vast majority of the roster has never downed the physical Cardinal.

“It’s definitely in the back of your head,” senior safety T.J. McDonald said. “You never want to end your career knowing that you didn’t beat a team.” After all, USC’s senior class is 0-3 against the Cardinal.

Without former quarterback Andrew Luck, who in his career terrorized the Trojans defense with his arm and his mobility — rushing for 137 and two touchdowns on 22 carries in three meetings, running back Stepfan Taylor is the Cardinal’s 2012 offensive headliner.

Though quietly operating in Luck’s shadow for most of his career, Taylor is one of the premier running backs in college football, boasting consecutive 1,000-yard rushing seasons, while often splitting duties with multiple tailbacks.

“They’re going to run to set up the pass game,” said sophomore linebacker Dion Bailey, who intercepted two passes against Syracuse last Saturday.

To combat the multiple spread offenses it sees in the Pac-12, USC has re-adjusted the type of defender it recruits, preferring lighter, faster players who can defend in space. These undersized defenders will be tested against Stanford’s more traditional pro-style offense that prioritizes tough blocking up front and running between the offensive tackles.

“I have to be fundamentally sound,” Bailey said. “I have to know where I’m supposed to be, so I can use my speed to my advantage.”

Junior quarterback Josh Nunes — Luck’s replacement — is off to an uneven start in 2012. Through two games, he has posted a respectable four-to-one touchdown-to-interception ratio, but has struggled with his accuracy. The Upland, Calif. native completed a pedestrian 53.3 percent of his passes last Saturday against Duke.

“You’re not going to be the same anytime you lose somebody people talked about as one of the best prospects to ever come out,” Kiffin said. “They seem to have relied on their running game, which is still really good. The offensive line, even though they had a couple of guys leave, is still a really good offensive line.”

On defense, Stanford’s physical and veteran linebacker corps is its most imposing unit. Chase Thomas, a 2011 All-Pac-12 first-team selection, and Shayne Skov, an explosive pass rusher who missed most of 2011 because of a knee injury, will pressure senior quarterback Matt Barkley to release his throws quickly.

Unfortunately for Barkley, USC might be without senior center Khaled Holmes, a three-year starter and his former teammate at Mater Dei High School. The offensive captain exited the Syracuse game on a stretcher after sustaining an apparent ankle injury, and his status for Saturday is unknown. USC does not release injury information, per a new program policy.

“It pushes me more to try to step up and get this line going,” junior offensive tackle Kevin Graf said of Holmes’ injury.

In his absence, the mostly likely candidate to start against Stanford’s tenacious defensive front seven would be redshirt freshman Cyrus Hobbi, a heralded four-star recruit from Scottsdale, Ariz.

“It’s always tough to watch guys go down like that, but we have Cyrus and he stepped up,” Graf said. “I know he’s ready for it if his time comes.”

With the first away game behind them, the Trojans expect fewer distractions and more consistent performance at Stanford Stadium.

“Getting that first [road win] out of the way is big,” Kiffin said. “We always talk about the first time going [off-campus]. As a team, every year is new when we travel and go on the road. Players need to understand our expectations. Hopefully, we play better this week.” Saturday’s game will kick off at 4:30 p.m. and be televised by Fox.