1. Fear of the unknown: Despite struggling to win games the past couple of seasons, the 49ers have won six consecutive season openers. Sunday they'll try to win an opener with a different coach for the fourth consecutive season, and no doubt that unfamiliarity has worked to their advantage.
The good news as far as the familiarity factor goes is that this new coach is none other than Kyle Shanahan, who faced the Panthers twice each of the past two seasons as the Falcons' offensive coordinator. That's also the bad news because the Falcons totaled 101 points in their last three games against the Panthers.
"He got us the last three times," linebacker Luke Kuechly said. "He's been creative the last three times and has had something new for us. That's what makes him good is that you can't dial in on exactly what he's doing."
But concerns about handling the unknown cut both ways. The Panthers plan to feature a tweaked approach on offense this season, yet in the preseason they showed very little with Cam Newton under center for just one series. The Panthers also have a new defensive coordinator, though it is a familiar face in former secondary coach Steve Wilks. In new roles, Shanahan vs. Wilks is an intriguing matchup.
2. Running men: Both offenses are capable of springing some outside-the-box plays, but the Panthers need not forget the value of running the ball inside the tackle box. Power running has long been a staple for this offense, and it certainly was last year when Carolina racked up 176 rushing yards in a Week 2 victory over the 49ers.
Running back Christian McCaffrey will make his NFL debut Sunday and could be a big factor in the new looks the offense flashes, but don't forget about stalwart Jonathan Stewart. He could well be the tone setter in this game.
3. 49ers can run, but can't Hyde? San Francisco running back Carlos Hyde is a dangerous weapon when healthy. In his first three season openers, he's averaged 101 rushing yards per game. But last year in Week 2, the Panthers did the job on Hyde, holding him to 34 yards on the ground.
What happens along the line of scrimmage should key whether it's Jekyll or Hyde in this one. Defensive tackle Kawann Short enjoyed a dominant preseason, and the rotation is stout – though the availability of Vernon Butler is in doubt.
But the middle of the 49ers' offensive line is a question mark as well: Appalachian State product Daniel Kilgore has been with the 49ers since 2011 but was the primary starting center for the first time last season. Guards Brandon Fusco and Zane Beadles have significant NFL experience, but Fusco is in his first season with the 49ers and Beadles is in his second.
4. Panthers' gold rush: San Francisco's offensive line does feature five-time Pro Bowl left tackle Joe Staley, a challenge to be sure but one that defensive end Mario Addison is embracing.
"I've got my work cut out for me. I'm going to have to give him the business," Addison said. "They throw me in that fire, I am going to bring that fire."
The Panthers ranked second in the NFL in sacks last season even with Addison leading the way with a modest 9.5 and even after a slow start to the season. With Julius Peppers added to the mix, the Panthers believe they can start fast this season and put quarterback Brian Hoyer's mobility to the test.
5. If it comes down to a kick: The Panthers go into the opener in the unique position of having two kickers on the roster, but head coach Ron Rivera confirmed that incumbent Graham Gano will get the call over rookie Harrison Butker.
"He's had a good week of preparation," Rivera said. "He's a veteran. He's had a lot of success. We're counting on him."
Gano missed two field goals in the preseason, though both were 50-plus-yarders that banged off the upright more than halfway up. The last time the Panthers played at the 49ers, in 2013, Gano's 53-yarder spelled the difference in a 10-9 victory in a marquee matchup of eventual playoff combatants.
The 49ers are going with veteran Robbie Gould, who kicked for the Bears from 2005-15. Last year in 10 games with the Giants, he made all 10 of his field goals.
LAST TIME THEY MET
View the top photos from Carolina's win at home by team photographer Melissa Melvin-Rodriguez.