Offense
Learn which types of run plays work best against each defensive front. For example, inside run plays are best to attack 3-4 defensive fronts. Outside run plays are usually more effective against the 4-3 defense.
If nothing develops on your outside run plays, don't be afraid to cut back inside and pick up what you can. Don't try to make something happen and end up losing yardage. Patience is key to the running game.
If the running play has a fullback, follow him through the designated hole. He will often break open running lanes for you to pick up yardage. As soon as you see some daylight, use the juke or spin move to get into the open field.
When using the pinch slide protection you may need to leave a running back in to pass block to the outside. The offensive tackles will block inside leaving the outside pass rushers unblocked.
Calling plays from Twin formations is the simplest way to tell if your opponent is in man or zone coverage. This only works against base defenses like the 4-3, 3-4, 4-4, 46 or 5-2. If the cornerbacks line up on the same side as the twin receivers, then it is man coverage.
When you are in the Red Zone and it is only first or second down, get outside and throw the ball away if nothing opens up. There is nothing worse than throwing an interception in the end zone when you are so close to pay dirt.
Defense
The quickest way to get the quarterback is right up the middle. Having defenders coming up the gut will put fear in most quarterbacks and make them get happy feet. When they see this type of pressure they tend to throw hurried, inaccurate passes.
Overload blitz schemes are effective because they put more blitzing defenders in one area of the field than the offense can block. Using shifts and manually moving defenders are the standard methods for creating overloads.
Look for defensive plays where linebackers are blitzing the A and B gaps. The linebackers are more aggressive at attacking the inside run gaps than if they were playing in man or zone coverage.
Many players like to control one of the safeties to defend outside runs and the option. Human players with good stick control on defense normally do not fall for fakes like the CPU AI defenders do.
As a general rule, zone defenses are better at containing the mobile quarterback than man defenses since the defenders are not chasing receivers all over the field. Instead they keep themselves facing forward and are able to keep an eye on the quarterback.
Don't put slow defenders in QB Spy such as defensive tackles when you are going up against a fast quarterback. A good mobile QB will simply outrun them. You are better off having them rush the passer or dropping them into zone coverage.