Sounds like old NCAA you had to run nickle fire man, spread the line and pinch... works every time... then run robber when they think they got you figured out..
It honestly seems to depend on who you are playing. If they have a QB that can run you need to play zone and bring zone blitzes to pressure the QB and as run blitzes. You have more options against teams with QBs that can't run. Which, shocking as it is, is kind of like the real game.