Well, I wouldn't consider myself a defensive master by any means, but I'm usually shocked when someone puts up more than 20 points on me.
So here are my suggestions and what works for me, some are pretty obvious though..
1. When picking the play, let the opponent pick first and then look at the box that tells you what they're putting on the field. Example: 2 WR 2 TE 1 RB and pick your defense accordingly. If they have 3 WR's, you might want to take a nickel defense. If they have 4, you might want to take a Dime defense etc etc..
2. I only run zone defenses when I'm blitzing, sometimes I run man, but not much. I especially like running LB and / or Safety spy when blitzing. Which brings me to #3..
3. Blitz, but not everyone. Get used to flipping your defense through audibles and paying attention to how the O-line lines up. If there's one tight end, blitz from the side the TE isn't..
If you want to hurry the QB into throwing quickly, choose a 4-4 and make sure your fastest LB's are on the outside. In this situation, I like 4-4 Cover 3. Then when you line up, choose the OLB that has a chance to get in the backfield without being blocked. Then line him up with the defensive linemen and move him out some like he'd be covering a WR. When the ball snaps, run him at an angle to the QB. Sometimes the RB blocks him, but if the QB is in shotgun, you have a great chance at sacking him, if not, it will hurry him to make a choice and your zone might get an INT.
4. Double up on the WR's and pull a quick D-linemen off the line into coverage for TE's or RB's. Sometimes, I like to take my DE's and pull them back bumping the TE's or RB's since they're a likely target when the 2 WR's are doubled teamed. Sometimes they'll complete a pass anyway, but most of the time, it results in a short yardage pass, an incompletion or a INT or coverage sack.
5. Change your defensive audibles and include at least 3 blitzes. Let your friend see you in a Dime prevent and then switch to 4-4 mad blitz right before he snaps the ball. You have to time that out right though. Or do the opposite, show blitz and then switch to a cover 2 man or something. Mix it up so that he's never comfortable with what you're doing. Sometimes I go through 3 defensive audibles while my friend is toying around with movement and snap count. It's really effective if you R2 and show him what you're in and then swich it up at the last second.
6. Slide a DE out and away from his blocker. This puts your DE in the backfield almost every time. Which is helpful with shotguns or RB tosses to that side.
7. Get really good at moving your D-line with L1, your secondary with triangle and your LB's with R1. Tighten them up, make your secondary play tight man and move your LB's left, right or spread where the situation calls for it.
8. When all else fails, right after your friend snaps the ball, knock the controller out of his hands and continue to sack him.