I'm not an expert, but I put up big numbers through the air using a spread style O. Using UNC, I had to find some type of fit for my offense, seeing as their O ratings aren't amazing, but here's how I set the depth chart up.
PERSONNEL:
I put Bryn Renner in due to his accuracy rating being higher than Yates so he doesn't overthrow as much.
I start Shaun Draughn due to his acceleration, and have Giovanni Bernard at backup.
I keep Pianalto at TE because of his catch rating
At WR, I like to have Little at the 1 with his 90 catch rating and his 87 route running. I put Jheranie Boyd at the 2 and Highsmith in the slot at the 3. I like having Highsmith there to make a mismatch, whether its a nickelback on him, or an LB on him, he gets open on a lot of routes. I keep the 4, 5, and 6 the same.
CONCEPT:
Now my concept to the spread, is mismatches. So even though I set my depth chart up that way, it doesn't mean I don't change things during the play. I run Notre Dame, and use Tight Slots and Trips Open as my base sets. Tight Slots puts your #1 WR at the #2 spot, creating a mismatch against that corner in man coverage. Trips Open can create an enormous amount of mismatches when using packages. My favorite one to use is WR Strong. This puts my #1 WR in the slot, and my #2 WR at the #1 spot. Now I have Jheranie Boyd at the #2, but in the regular depth chart, he'd play the slot. This makes the #1 CB ineffective as I won't be passing toward his way. With this, I would either run a play as is, or audible into Tight Slots. This will throw your opponent off and have him audible into something else as well. Now that you have your opponent off guard, it's time for you to make the correct reads.
MAKING THE RIGHT READS:
To make the right reads, you have to be able to read the defense. Reading the defense isn't a hard thing to do. Just look and see whether they are in man or zone, and whether they are pressing or not pressing. Looking for the blitz is a bit more difficult, but if you can see the blitz, you're going to need to make a quick read after the hike. By doing this, you'll need audibles set up to adjust to your opponent. All of my audibles but 1 are set up out of Shotgun.
I try to pick plays that aren't used as formation audibles so I can have a total of 25 audibles to throw my opponent off. I also like to try to make plays out of the formation audibles. This will make your opponent re-think their whole defensive gameplan, putting you in the driver's seat. Also try to read the personnel. You could have a WR lined up on a LB and not realize it until it's too late. If you see this, try to put the WR on a quick route and get it to him before your opponent can react.
KNOW THE ROUTES:
You HAVE to know your players routes. By doing this, you can be 1-step ahead of your opponent. If you don't know the route, then you and your opponent are essentially at the same place, but when you can remember the routes, you can scan the field in 2 seconds and make your read.
By doing these, you don't need a certain 5 plays to run in a game, and can have variety in your spread attack. This makes you a bit more deadly when coming out of shotgun vs any set.