Autosubs have a massive gameplay impact (as do the gameplay assist options). If you don't know if a setting affects gameplay, assume it does.
EA calibrated the game on All Pro default (default meaning the assists turned on, CFM autosubs at 49/50, and everything else at default). As you play a few games, it becomes readily apparent that this is how the game was built....and it is quite good.
Just dive-into some regular season games, have some fun, and don't worry about things....let the games play out. As long as you don't cheese, you should have some terrific ratings-driven variety.