1. I really don't look for a defense in particular on pass plays. What I do is remember my GO-TO-GUY's route (highlighted in Orange). Then once I snap, I look to see if I have a blitz on my way. If they do blitz, then I look for a quick route up the middle, or escape route. If there's no blitz, I go back to my GO TO GUY and see if the saftey or LB's cheat into the zone he'll be in once I pass. It's really all instinct. But I would say work on that. If no one's open, dump it off to a flat or a delayed check down route.
2. Hot Routes, you pick up a blitz, then route a receiver to the middle if it's a LB, or an out and up if it's a safety. Look for your mismatches and adjust accordingly. That's why I play with 9-10 min quarters to allow my reads to settle in.
3. I only go deep on one-on-ones. Double coverage is only an option for obvious desperation moments.
4. Switch your packages up before you select a play. Move your impact or star players into the go to position to maximize your opportunities. In one of my dynasties, I use Graig Cooper as a wideout as well. If you have a star WR, put him as an HB time to time on rushing plays. If you have a star TE, package him in as a slot end. Use a team like Gators and Percy Harvin as a great example.
5. I choose one set to audible from, and set all my audibles from there. I usually go with a Pro Set or I Formation as it provides good balance of both audibles.
6. Motion to get more blockers on run plays. And make sure if you do motion someone over to another side, hot route them to block on side the run is going to. Ex. If your motioning a TE from the right side of the line to the left because you're running left, he'll still keep his original assignment of blocking on the right but houte route him to block left. Trust me, there is a difference.
On defense, just mix up you're play calling in the right situations. You don't necessarily have to use a Dime or Nickel if the O comes out with 4 or even 5 wideouts.
Also, use packages to keep your best players in the game at all times. In year two, Sean Spence is my best LB but he plays OLB. On dime plays, I change the package to allow him to be the primary LB.
Recognize your strengths. Mine are my LBs. Sean Spence, Arthur Brown, and the #1 incoming frosh LB, James Latimer are the anchor of my defense. I keep them all on the field as much as possible. Spence is quick to cover the whole field. Brown is my anchor in the middle. And Latimer is a sure-fire tackling machine. I even let package my LB's into the line as well on dime plays.
This is it for now. I know there's more and if they come to mind, I'll be back to post. Have fun.