For starters, Arizona's offensive line is in disarray. As Pro Football Focus details in its preview, every member of the offensive line is performing near the bottom of the league at their respective positions (with the exception of left guard Daryn Colledge). Last week, the Minnesota Vikings got seven sacks against Arizona on 69 offensive plays -- and the Vikings didn't send one blitz.
John Skelton will have to rely on quick-hitters and bubble screens, with another big game from running back LaRod Stephens-Howling, to move the ball against San Francisco's vaunted defense. The 49ers are ranked No. 3 in DVOA (explained here) by Football Outsiders -- No. 6 against the pass and No. 5 against the run, so there's no glaring defensive weakness. Aldon Smith, Justin Smith and the rest of the 49ers' defensive front will likely be able to generate pressure on Skelton without blitzing.
However, the Cardinals have an elite defense as well. Arizona's D is ranked No. 5 in DVOA, but is stingier against the pass (ranked No. 4) than the rush (No. 13). That could be a problem against Frank Gore and a 49ers rushing attack that is second in the league, averaging 176.6 yards a game. If the Cardinals can't keep this game close in the first half, it could be over quickly. They aren't a team built to play from behind and grab a back-door cover.
This season, the 49ers are 4-3 against the spread and are covering by an average of 4.2 points. The Cardinals are 3-3-1 ATS, covering by an average of 2.7 points. According to ESPN Insider's PickCenter, the public is split almost evenly on this one, with 50.3 percent favoring the Cardinals.
Matchup: San Francisco 49ers at Arizona Cardinals
Spread: Opened at 49ers minus-6.5, now at 49ers minus-7
Total: Opened at 37, now at 38.5