Superficially, the match up on defense looks very challenging for the Giants. The Giants defense against the run has been poor this year and the 49ers running game is their strength on offense. However, it's not as bad as it seems, IMO. First of all, the Giants defense seems to be getting a little better as the season is moving along. Second, the teams that have run best against the Giants are the ones that have spread their offense out, gotten the Giants in nickel coverage, fooled the young/light LBs and gashed the Giants for a few long runs in each game. It's almost more encouraging for the Giants to have totally blown one or two plays in each game than to have given 5-6 yards on every play. While Frank Gore does have some speed and can make a long run, he is more of a power back and the 49ers are not a spread-the-field offense. Giants DL is pretty good against the run, especially with Tuck back and starting to play a little better. The hope here is that the LBs will play better also with the experience they have gained over the first half of the season and Giants will at least make a representative effort against the 49ers running game.
Manningham hurt his knee, apparently in practice this week and has been added to the injury report. It looks like Nicks is coming back and with Barden able and ready, Giants should still have enough weapons for Eli to throw to. Barden only made two catches against the Patriots in his 2011 debut, but he looked very good to me - big and powerful for a WR - and he ran his routes very smoothly.
I might have Webster keeping an eye on TE Vernon Davis, who might be the 49ers biggest down field threat and is a physically bigger target than Crabtree. Webster has great size and can battle him.
Giants need a big game from their front 7 to stop the running game and from their OL to counter the strong 49ers front 7. If they do they will be able to make a game out of it. If Osi is not handling the run well, Giants should not be afraid to get Kiwanuka up front and replace him with another LB.