1. Pass Rush
To me, there's nothing bigger to watch than the pass rush and I don't think there will be anything that has a bigger impact on the result of the game than the Colts pass rush. Last year, the Colts/Broncos game changed because of great pass rush from Robert Mathis. This year, Mathis is suspended for the first four games and will miss this one. Making matters worse is that last year Mathis accounted for nearly half of his team's sacks (an insane number). The Colts desperately need someone to step up this week and pressure Peyton Manning. The problem is that Manning will pick apart defenses if they try to blitz him, so Greg Manusky is going to have a decision to make. The best way for the Colts to produce pressure with Mathis out is by different blitz schemes, which we saw in the preseason and which worked. But Colts fans should know better than anyone that blitzing Peyton is a very risky game and normally doesn't work out well for defenses at all. Ideally, the Colts wouldn't have to blitz too much. Ideally, Bjoern Werner would step up in a big way. The Colts absolutely need him to. Last year's first round draft pick had a good training camp and preseason, and the it's crucial that he steps up and gets some pressure. If Werner has a good game Sunday night, the Colts chances of winning would go up in a huge way.
2. Offensive Philosophy
If this game were the opening game last year, I could already tell you the way Pep Hamilton would call it: a balanced mix of running and short passes early on as the team tried to establish it's run game, then after they were down by a couple of scores they'd table the efforts to try to establish the run until the following week and let Andrew Luck loose to go win them the game. It happened too much last year. We should see right away just how much Pep Hamilton really has improved. Will he run the no-huddle shotgun offense at the start of the game? Will this offense be predictable? And how much will they let Andrew Luck do from the get-go? Those are questions that, depending on their answers, could prove to be crucial to the Colts' chances this Sunday. I'm not advocating at all that the Colts need to not give Richardson carries, but they need to mix up the offense and run it more around Luck this year than it was last year. And on Sunday night, they need to let Luck loose from the beginning before they fall behind too much, because this is one game I'm not sure the Colts could come back from a huge deficit in.
3. Offensive Line
You already know about the offensive line questions the Colts have. At the same time, most of those questions are related to depth. Outside of the center position, the Colts currently have just two depth linemen that will be healthy for the game: guard Lance Louis and tackle Jamon Meredith - who the team just signed earlier this week. When it comes to the starters, the line doesn't look nearly as bad, though there are still question marks. First and foremost, who will start at center? With Khaled Holmes practicing both Wednesday and Thursday his chances are looking much better, but then also Jonotthan Harrison has returned to practice and A.Q. Shipley is capable too. The Colts have options at center, but if he's healthy Holmes will be starting. If he does, we'll be watching closely to see how he does. And then rookie Jack Mewhort will be starting at left guard, so he'll be a player to watch closely as well. And as a bonus, we'll be watching right guard Hugh Thornton to see if his preseason improvement will last (I think it will, which is a good thing). I don't think the line will be the disaster some are fearing, but it'll certainly be a focal point this Sunday night.
Going up against Peyton Manning isn't an easy task. Doing so without a great pass rush (see point number one) is even harder. Yet that's precisely what the Colts secondary will be asked to do on Sunday. Vontae Davis, Greg Toler, and Darius Butler will be the three prominent corners and then LaRon Landry and Mike Adams will start at safety. Believe it or not, this secondary can match up with the Broncos receivers. And they play a physical game, which helps their chances of beating Manning. You're not going to get into Peyton's head, but if you can disrupt his receivers then you'll disrupt him. The offense is so incredibly predicated on timing that physical play from the defensive backs is the way to go. Of course, the Colts will likely get some flags thrown on them and they'll likely get beat on some plays, but they need to weather the storm and continue to play physical. If they can do that, they'll have as good of a shot as possible to stopping these receivers without much pass rush help. I don't envy the job the secondary has to do on Sunday night, but I don't think they're unprepared or even necessarily outmatched.
5. Andrew Luck
Of course Luck is on here. If the Colts hope to win on Sunday night, they'll need their quarterback to play well. Luck will likely take to the air a lot against the Broncos (both because that works best and because they'll likely be behind at least at some point in the game). For the Colts, that's a good thing (see point number two), and Luck can handle it. But of course he's a player to watch because he's just so important to this team.
Editor's Note: SB Nation's partner FanDuel is hosting a $1,000,000 Fantasy Football Contest for Week 1's NFL games. It's only $25 to join and first place wins $100,000. Starts Sunday, September 7th at 1pm ET. Here's the link. FYI: These are just my opinions and Fanduel gave me money to play.