To me, there are 2 huge things to be worried about this week.
1) Of course Peyton Manning and all he can do. I don't think we can play a vanilla defense against him because I'm not sure our DL can put enough pressure on him. And the Colts have several playmakers on offense (Wayne, Clark, and the up and comers in Brown and Garcon). We have to speed things up somewhat or he'll pick us apart all game. Of course he is as good as anybody when it comes to countering what the defense is throwing at him. He can recognize a blitz and audible very easily. I'm not sure how we'll attack that offense, but it will definitely be one huge factor in the game.
2) The Colts DE against our OT. This one scares the living crap out of me. In last night's game, the Dolphins were able to manage them somewhat by running some draw plays at them and by giving the tackles help on drop back passing plays. But when the Dolphins had to move the ball at the end of the game and no help was given, the pressure was there. Last season the Cards were hesitant to give the tackles any help because it reduced the number of receivers in play. I don't see how we can leave the tackles alone against these guys. They are both very fast around the corner.