I think Spike, in his comments, had it right. Peyton Manning should throw all over the Saints' defense. The Saints D is ranked 26th in the NFL, and Brett Favre picked them apart though they had a couple of key ints. The Saints have some good players on defense in Jonathan Vilma, Darren Sharper and Tracy Porter along with some others, but Peyton and his wrs Reggie Wayne, Dallas Clark, Austin Collie and Pierre Garcon are almost unstoppable. I just don't think the Saints can stop them. Their best chance is to put a ton of pressure on Peyton with a variety of blitzes. Still, he is a master in stepping up in the pocket, avoiding pressure and in reading defenses. It'll be tough.
New Orleans can definitely put points on the board. Their oline is good at protecting Brees and Brees is an outstanding qb. Plus they have a better running game than the Colts. Pierre Thomas is a quality back and Reggie Bush adds some big play ability in there. The Saints receivers, though not as good as the Colts, are good. They dropped a couple against the Vikings, so they can't afford to do that against the Colts.
It's hard to go against Peyton playing against, up to this point, a vulnerable defense. The Saints will really have to step it up on that side of the ball and create some turnovers like they did against the Vikes to have a chance. They were pretty good at the end of the game against the Vikes. Their pass rush will be critical.
Drew Brees needs to play the way he has all season. He has been incredible, just like Manning. Right now though, the Colts look pretty good.