(Courtesy of CBS)

Bills at Cardinals -- Week 6

Where: University of Phoenix Stadium, Glendale, Ariz. (grass, indoors)

When: Sunday, 4:05 p.m., ET (CBS)

Spread: Cardinals by 4.5

Records: Bills (Overall: 2-3, AFC East: 0-2); Cardinals (Overall: 4-1, NFC West: 1-1)

Past results: Two most recent meetings -- Oct. 5, 2008: Cardinals 41, Bills 17; Oct. 31, 2004: Bills 38, Cardinals 14. Series record: Cardinals lead 5-4.

What matters: The balloon has been popped, the party is over and the streamers have been put away. Someone put a cork back in the champagne. Arizona's date with destiny was dashed in St. Louis on a Thursday night grand stage, and the Cardinals will have had 10 days to stew. Now the defense is angry, the offense is eager to regain its footing, and the focus is not on perfection, but simply getting back to winning ways. Against a Buffalo team that was lambasted 45-3 by the San Francisco 49ers, it could happen sooner than later.

Who matters: Running backs LaRod Stephens-Howling, William Powell, Alfonso Smith. The scarcely seen, little-known trio is thrust into the limelight with the loss of Ryan Williams for the season. With Beanie Wells already out with turf toe, and the Cardinals choosing not to add a running back on the market, Stephens-Howling becomes the team's feature back for the first time since a one-game honeymoon in Week 17 last year. Powell, the NFL's leading preseason rusher, and Smith should see roles in the offense, as well. 

Key matchups: Buffalo DE Mario Williams vs. Arizona OL: Williams, the Bills' $16-million man, has been more like the Hollow Man this year. With a total of 1.5 sacks in five games, after registering five in five games last year before being sidelined for the season with a torn pectoral muscle, the talk is Williams has a bum left wrist. The Cardinals' woeful offensive line might be just what the doctor ordered. Arizona surrendered nine sacks against the Rams.

Injuries of note: Wells and Williams are clearly the most damaging, as a duo. The loss of tight ends Todd Heap (knee) and Jim Dray (knee) has been dampened by the emergence of Rob Housler. CB Greg Toler (hamstring) could be missed if Ryan Fitzpatrick regains his footing.

Inside stuff: The decision to sign cornerback Crezdon Butler, rather than a new running back to help supplement the wounded corps, speaks volumes to both positions. With Toler and backup Michael Adams likely out against the Bills, Butler was signed to bolster the defense against a pass-happy attack. But it also signifies Whisenhunt's confidence in his running backs, despite their relative anonymity.

Connections: Former Bills QB Frank Reich coaches Arizona wide receivers, while Bills offensive coordinator Curtis Modkins formerly coached the Cardinals' running backs.

Stat you should know: Arizona quarterback Kevin Kolb was sacked 17 times the last two weeks. Against a Buffalo defense starving for some big plays up front, he could be on the run once more.

Looking ahead: This game might well be considered a must-win, giving the brutal gauntlet the Cardinals must pass through over the next four weeks, with a road trip at Minnesota, followed by a home date with San Francisco. Then, back-to-back landmines at Green Bay and Atlanta.

Prediction: Cardinals 20, Bills 17

For more news and analysis from Cardinals blogger Jon Gold, follow @CBSSportsNFLARI on Twitter.