The 49ers have certainly struggled at times against running backs with decent hands in part because they've faced some very intriguing weapons out of the backfield. Against the Saints they had to deal with Reggie Bush, who is always a home run threat, and Pierre Thomas, who currently ranks seventh among NFL running backs with at least eight targets. Against the Kansas City Chiefs they had to deal with Dexter McCluster and Jamaal Charles who are both crazy athletes that can be tough to stop in any fashion.
The Raiders certainly have a great receiving back in Darren McFadden. Marcel Reese and Michael Bush also seem to be involved in the passing game but McFadden is the guy that concerns me most. While he's really shown his abilities in the running game this season, his role as a receiving running back has always been top notch. The 49ers biggest problems come with athletic running backs. Obviously all football players are athletes, but certain running backs come across as a bit more athletic than others. The 49ers struggles are against these guys.
One of the 49ers biggest problems this season has been poor tackling. Players have slipped away from the 49ers defenders with relative ease and made them look incredibly sloppy. More than anything the 49ers need to tighten up their discipline and wrap up players when they get the first opportunity.
As far as specific players that will be involved, I'd imagine we'll see Manny Lawson covering Darren McFadden a fair amount this Sunday. Lawson generally draws some of the more athletic players and will get his chance at McFadden if McFadden is playing on Sunday (I'm assuming he will be, but he was limited in practice today). That could be one of the more interesting matchups to watch on Sunday.
The 49ers also made a change in their secondary by inserting rookie Taylor Mays in as the starting strong safety. He's a solid tackler but he struggles in coverage. If McFadden, or any Raiders running back (or receiver for that matter) gets deep in his territory, it could be troublesome. Mays is a very up and down player, although he's much more athletic than former starter Michael Lewis. Mays is learning week by week and will certainly have his up and down moments.
In my research it sounds like Jason Campbell likes to use the tight ends a lot. I'd like to think that could extend to the running backs as well on checkdown routes. I could be entirely wrong on that, but if Campbell does in fact start on Sunday this RB/pass defense matchup could very well be the most important matchup of the game for the Raiders offense.