It depends on how they are being used...
What type of runs are they using?
Zone runs, power runs, misdirection, or isolation?
What type of passes are they throwing?
Deep, medium, or short?
Where does the passer setup?
3-step, 5-step, 7-step, or rollouts?
How does the defense defend?
Man, zone, blitz, or combinations?
Always look at the number of the player that makes the plays and determine if you have a matchup advantage somewhere because of it. For example, if you're sacked by a guy with a number starting with 2-4, the secondary is a player shorter than a normal coverage. Keep someone in to block so you can take advantage with a deep ball. If his number starts with a 5 or 9, look to his your TE.
The key to winning is adjusting to tendencies... that said, the CPU doesn't have tendencies.
Later