what difficulty level do you play on and do you play online?
stick with one D, if you use Cowboys you should use the 3-4 playbook
just match up corners with recievers unless you think its gonna be a run, if you are gonna blitz, audible to jam the recievers and send an outside linebacker on a blitz if there is no tight end on his side, or even if you are in nickel or dime send a corner cause they are the fastest on the defensive side of the ball. Alot of it is anticipating what your opponent is going to do.
If you are having trouble stopping the run, stay in man D and whoever is on the RB, user him and right after the snap, hold down the A button and it will follow him. But when I use cowboys I user Ratliff and swim through blocks to either get to the QB or the RB if he goes in between the tackles, if its a pitch or toss, I switch to the DE or OLB and tackle him.
Thing is with man you can get burnt by screens, so having some sort of contain play (I use 4-3 playbook, Dime Flat contain for this) to either pick it off or stop him in his tracks.
As for pass D, its best to user a DE straight away and get around the tackle (swim don't sprint and once you are in the clear, hit A and it will go straight to the QB), best to use the LE because most QB's are right handed and have their best pass blocker as the LT. Just check his power/finese move ratings.
If you don't get enough pressure, the QB will eat and exploit any zone D, so always send an extra blitzer. I like cover 2 sink for zone D, or if they are trying to conserve the clock, cover 3 or cover 2 is good as it has alot of protection on the sidelines.
Also, if you don't get their in time, with your DE, wait till after the QB throws and if your DB or whoever is near him, change to him at the last second and press SWAT or CATCH, but only use CATCH if you know you can pick it otherwise its a TD.