I have sliders for Def Help, On Ball Defense, Hustle and Hands all maxed out, which makes driving and lead passing a bit harder.
Also, it seems like the Defensive Pressure setting under Coaching Profiles messes up rotations when set really high.
If there are too many lead passes for easy layups because of the AI doubling the PnR ball handler, I'd leave it around 50 for all teams and adjust individual defensive settings for the AI, because Auto isn't too smart.
I do this before every game and while it's not perfect, you can improve defense somewhat.