Giants at 49ers -- Week 6

Where: Candlestick Park, San Francisco, Calif. (grass, outdoors)

When: Sunday, 4:25 p.m. ET (Fox) Spread: 49ers by 6.5

Forecast: Partly cloudy with high of 69 and a low of 54. Mild, no precipitation in the forecast.

Records: Giants (Overall: 3-2, NFC East 0-2); 49ers (Overall: 4-1, NFC West 0-0)

Past results: The Giants and 49ers split two games at Candlestick in 2011. San Francisco won in Week 10, 27-20, and New York won the NFC Championship Game in overtime, 20-17. Series record: This is the 29th regular-season meeting between the two teams and the series is knotted at 14 wins apiece.

What matters: The 49ers' top-ranked running game could have ramifications in all areas on Sunday. If San Francisco can run at will, they’ll end up owning the clock, and that would limit what New York would be able to do on offense. The Giants have rediscovered their running game (Ahmad Bradshaw had his first-ever 200-yard game last week), so it would be a shame if they had to ignore it because they only had time to pass. Yes, New York’s receivers are getting healthy again, but coach Tom Coughlin craves offensive balance because it keeps defenders on their heels. But unless the Giants’ 16th-ranked run defense is up to the challenge, the offense won’t get that chance.

Who matters: This is Eli Manning’s game as much as anyone’s. He’s been in two high-pressure games with the 49ers in the last year, throwing two crucial picks in a Week 10 loss and pulling off an overtime win in San Francisco in the NFC Championship Game. Regardless of whether he has wide receiver Hakeem Nicks (questionable, knee/foot), Manning has to do what he does best, which is taking what the defense gives him. San Francisco’s defense ranks second against the pass and seventh against the rush, so Manning has his work cut out for him. Keep an eye on check-down options like fullback Henry Hynoski, running backs Ahmad Bradshaw and David Wilson as well as tight end Bear Pascoe. Tight end Martellus Bennett (probable, knee) should play, but Pascoe can be used for added pass protection and some shorter routes. Manning and the Giants need all hands on deck if they’re going to get the best of what might be the league’s best defense.

Key matchups: Wide receiver Victor Cruz said he’s sick of answering questions about 49ers cornerback Carlos Rogers. The inquiries stem from Rogers’ version of Cruz’s salsa dance in Week 10 last year, but these two guys could actually end up deciding the game. With Nicks’ status up in the air, Cruz is left as the Giants’ primary big-play threat. He had 16 catches for 226 yards in two games against San Francisco last year, but Rogers had two picks in the 49ers’ Week 10 win. Even if Rogers doesn’t guard Cruz exclusively, the two players will likely still get questions about one another.

Injuries of note: Nicks, right tackle David Diehl (knee) and safety Corey Webster (hand/hamstring) are all questionable for the Giants, who are already without safety Kenny Phillips (knee) and defensive tackle Rocky Bernard (quad). Tackles Will Beatty and Sean Locklear have played well in Diehl’s absence, and Webster is expected to play, but defensive tackles Markus Kuhn and Marvin Austin will need to step up.

Inside stuff: Linebacker Jacquian Williams told that he won’t defend 49ers tight end Vernon Davis, which probably means that assignment will be left to rookie nickelback Jayron Hosley, who is returning from a hamstring injury, and safeties Antrel Rolle and Stevie Brown. Brown, who defended Davis as a member of the Raiders in a few preseason games, said the key is keeping the All-Pro tight end in front of you. Davis has top-end speed, so defending him like a wide receiver may be the smartest route for the Giants.

Connections: Giants center David Baas played in San Francisco for six years and Pascoe was drafted by the 49ers in 2009 but didn’t make the team. Of course, former Giants wide receiver Mario Manningham and running back Brandon Jacobs play for the 49ers now. Jacobs has been injured, but he could play Sunday, and Manningham has been productive (19 catches, 186 yards). Manningham said he can coach up the 49ers defensive backs on the Giants' tendencies, but offensive coordinator Kevin Gilbride dismissed that, saying New York’s offense is predicated on what a defense is already doing. In other words, the Giants simply react to what an opposing defense shows them.

Stats you should know: New York has forced a turnover in 34 of its last 37 games, and that trend could be important on Sunday. The 49ers rank 27th in the league in passing, so they don’t take a lot of risks through the air, but that doesn’t mean it’s impossible get takeaways against them. Also, 49ers quarterback Alex Smith has a bad finger on his throwing hand, and that’s something the Giants defense has to be aware of.

Record watch: In Week 5, Coughlin (77-56) tied coach Bill Parcells (77-49-1) for second on the team’s all-time regular-season win list, so he’ll have a chance to overtake his former employer in Week 6. Steve Owen is the Giants’ all-time win leader with 151 victories.

Looking ahead: The Giants’ schedule doesn’t get any easier after Week 6. The Washington Redskins -- who beat New York twice last year -- visit in Week 7 before the Giants travel to Dallas in Week 8. The Cowboys beat the Giants to open the season and the Philadelphia Eagles beat them in Week 4, so wins in Weeks 7 and 8 would pull New York to 2-2 in the NFC East.

Prediction: Giants 33, 49ers 27

Follow the Giants and Alex Raskin @CBSGiants and @AlexRaskinNYC.