Gossip Girl: I want my friend back this will be easier done with serena out of the picture.

Chuck: I want my friend back - this will be easier done with Serena out of the picture.

He's not referring to Nate. He can always be friends with Nate even with Serena in the picture. It makes more sense that he is speaking of Blair.

He needs Serena to stay away in order to win her back. Chuck knows that if Serena returns she will act as a moral compass guiding Blair to stay away from the "bad" influence Chuck is based on her decision to trade a night with Jack in exchange for the return of his hotel. In order for her to stay in Florida Chuck is encouraging a rift between her and Nate so that she won't have any reason to return to quickly giving him time to get closer to Blair.

Blair's Moral Compass: I feel as if Blair is playing the part of Scarlett in the movie "Gone with the Wind" where she is attracted to good morals in an esthetic sense, while not truly believing in them. Blair and Chuck are not bound by the same morals as everyone else, it's what makes them so similar and spectacular.

http://www.youtube.com/watch?v=lSfniJXUC9E