I am going with default but have the game speed on fast and getting great results. Speed threshold on 50 as well. I also left the setting to have ball carriers do auto moves to elude defenders, that has brought the play making ability out more with rushers it seems.
Still having a blast with this game. I only control runners after they have the ball and will scramble with qbs if it is there but it's not a given you escape the pocke.
As for penalties I believe I have mine up by 5 clicks for default. Not seeing a lot of PI so may bump those up, but have see holding, offsides, false starts.