Get to Manning, ring his bell, and the Colts offense suffers as a result. It's as simple as that. When Edge wasn't himself following his knee injury the Colts offense suffered as a result though they did get better in their passing game when Edge was less effective. I'd say at this point the Colts can still do well if their running game isn't working. You have to take away their ability to pass the ball and that means either covering their recievers forever (impossible) or getting to Manning and making him hurt (difficult but possible).
I too am getting ready to join the "PLAY PEEK!" crowd. Results are results and as has already been noted we don't stop anyone from running on us anyway so how much of a dropoff in run defense could he be?