Try this for running (I haven't tested passing at all!!).
Penalties:
OS-99
FS-0
HLD-0
FM-30
KR/
PR-50
CLP-53
RTK-0**
Sliders:
RunBlk- 25/25
React/Int/PC- 50 for all
TKL-25*
*As you had already alluded to Josh, it seems like the lower the TKL the better angles taken to holes instead of blockers, but you don't want to be too low.
**Think I may have just discovered something with RTK. At 100 safeties are running 100mph to the line of scrimmage at the sign of a handoff. If they get blocked there's no one back there to play "safety" haha. At 0 you actually see guys take real pursuit angles worrying about where the ball carrier may be heading. This must be combined with KR/
PR, And TKL to see proper reaction and pursuit angles.
IMO no other sliders than these affect the run game on the defensive side of things.