1. Bob Sanders - The Colts safety may have the luxury of cheating up into the box to help with the run since the Titans passing game hasn't truly gotten on track as of yet. Titans running back Chris Brown used a lot of counter and cutback runs to get free of the chaos near the line of scrimmage, and since Tennessee usually gets an offensive lineman free to take on the middle linebacker on those types of plays, Sanders will need to be the primary inside run-stopper at the second level.
2. Reggie Wayne - All the buzz has been about Marvin Harrison going up against former Colts cornerback Nick Harper for obvious reasons. But the big plays may come on the opposite side as Wayne takes on second-year cornerback Cortland Finnegan. If safety Calvin Lowry doesn't do a better job of staying in sync with Finnegan on that side, Wayne could have a big day.
3. The Weak Side Linebacker - Freddy Keiaho is supposed to be a gameday decision due to a dislocated elbow. If he can't go, Tyjuan Hagler will likely step in even though he's been working as a strongside reserve for most of the year. Hagler, who was a weakside reserve last season, will have to switch gears from being more of a containment linebacker at the strong side and revert back to his roaming and more aggressive style of play that is needed at the weak side. Fortunately, Hagler is a quick, hard-hitting linebacker who may actually be better suited for the weak side. Whoever gets the start, he'll have to play a major role in hitting gaps to disrupt the flow of running plays while also keeping Vince Young from getting too far downfield when he tucks the ball and starts to run.
4. Ryan Diem - The Colts' right offensive tackle draws the assignment of blocking Titans DE Kyle Vanden Bosch, who is always a handful. Since QB Peyton Manning will be aware of left defensive end Antwan Odom battling rookie Tony Ugoh from his blindside, he can't afford to be distracted by pressure from Vanden Bosch to boot.
5. Peyton Manning - The Colts quarterback will have to be patient and smart as the Titans showed a stout run defense last week. If they succeed in forcing the Colts to become one-dimensional, Manning will need to spread the ball around through the air, taking what he can get underneath while exploiting one-on-one matchups.