Real Madrid's Cristiano Ronaldo has scored against Barcelona in all of the last six editions of El Clasico, which is a record. He's going to need to extend that record.
Real Madrid are not going to keep a clean sheet at the Santiago Bernabeu on Wednesday night. In many cup ties, the home side attempts to survive the first leg and deny an away goal before going all-out in the second leg, but Real Madrid will not have that luxury, simply because their defense is going to screw up. Without Pepe, Sergio Ramos and Iker Casillas down their spine, Madrid will surely concede against Barcelona.
So, they need to outscore the Blaugrana. They need to do it without Angel Di Maria, and likely with three somewhat defensive-minded midfielders in the center of the pitch. They'll have one less body in attack than they usually do. The front three of Cristiano Ronaldo, Mesut Özil and whoever starts at center forward are going to have to do a lot by themselves.
Of course, Gonzalo Higuain and Karim Benzema are more finishers than guys who create their own shot, while Özil is more of a creator than a guy who puts the team on his back and finishes off chances on his own. The only player on the pitch for Madrid who will be able to create for himself and finish for himself on a regular basis is Ronaldo, and Madrid will need him to pull a rabbit out of his hat on one or two occasions to win on Wednesday and head to the Camp Nou with something to play for.
His primary marker will likely be Dani Alves, who looks primed to start at right back for Barcelona. It's hardly news that Alves likes to bomb up the flank and is regularly caught out of position. He will need to be more disciplined than normal in this match, while Sergio Busquets and Carles Puyol will have one eye always drifting over to their right.
Don't be surprised if Barcelona go to a back three when they lose possession, with Busquets dropping back in between the two central defenders. Puyol is excellent at getting outside to close down the threat from the opposing left winger in this situation, while still remaining aware of his responsibilities in the center. The Barcelona defense will still get stretched if Puyol comes out too wide, however, so Alves will need to remain disciplined on the right.
Madrid's best chances to score are likely to come from counters that feature Ronaldo stretching out the Barcelona back line, then finding his center forward with a square ball. Ronaldo is also good at timing his diagonal runs between two defenders to get on the end of through balls by Özil, who is a genius at spotting that run and executing the pass. Ronaldo's ability to catch the defense out of position and act quickly to exploit it will be the difference for Madrid going forward on Wednesday.