I boxed for a long time. Even though people call boxing the "sweet science", it still usually comes down to two fighters looking to land their "right hand" while slipping their opponent's.
"Right hand" usually means right hand because most people are right handed and that's usually their best punch. The "sweet science" usually comes down to this. Of course there are setups and some fighters can land it in a number of different ways. Some fighters are even lefties. Some fighters develop power in both hands. Others learn to bait it in a number of different ways. The best fighters generally slip it and land it the best. Think Smokin' Joe.
How is Madden any different from this?
Defensively, find out what they want to do and either take it away or make them pay for trying to do it. Offensively, find ways to hurt the defense in ways that seem unassuming to them. Get them to defend one thing, then hurt them with something they either don't expect - or don't perceive as a threat.