I live in Indy, and am a huge Peyton Manning fan. I hope he absolutely lights it up this year and for every year as long as he's healthy enough to play. That said, I'm not drafting him in any of my leagues this year unless he is an absolute screaming value.
Why? Because if I'm going to take a chance on a guy in the middle rounds as my QB1, I need the upside to offset the risk enough to justify the pick. I don't think that's going to be the case with Manning this year. His health and conditioning questions aside, it's a new offense for not only him, but everyone else on the offensive side of the ball. I don't see how this magically turns into Top-5 production, and the worse case scenario is that he doesn't even perform at the same level as the guys around him.
If I'm waiting on my QB at that spot, I'm probably taking a guy like Ryan, who could clearly outperform his draft position, and the basement on him is most likely right around where you're drafting him. Very low risk, and decent upside.