REGULAR
For any 2WR formation
Definitely tag the rush QB (but actually check and make sure he don't pass a lot , too)
If the Scramble QB never passes (only runs or hands off to another runner)
use the 4-3 defensive formation
D-line bunched
Set your LB's to Spread, Have LOLB play flat zone strong, ROLB flat zone weak
Drop your MLB as far back as DPC allows and set to Spy QB
Put your FS and SS to the furthest edges of the field and about 8 yards off the LOS, blitz with them
put CB1 and CB 2 on cover man w/out move and pull them about 2yrds back from the LOS and just inside their respective receivers.
If the Scramble QB does pass sometimes:
use the 4-3 defensive formation
D-line bunched
Set your LB's to Spread, Have LOLB Cover manw/out move TE with end assignment of zone flat strong, ROLB set to cover man w/out move FB weak with end assignment of zone flat weak
Drop your MLB as far back as DPC allows and set to Spy QB
Put your FS to the furthest edge on the weak side of field and about 8 yards off the LOS,set to Cover man w/out move HB weak -or- Blitz
Put your SS to the furthest edges on the strong side of the field and about 8 yards off the LOS, set to Cover man w/out move HB Strong -or- FB Strong -or- Blitz
put CB1 and CB 2 on cover man w/out move and pull them about 2yrds back from the LOS and just inside their respective receivers.
That works pretty good for me in 2WR sets. But scouting reports may have me adjust the settings if I notice the scramble QB hands it off to backs whom then rush up the middle. Something as simple as changing my MLB's assignment(dropping Spy) and keeping the OLB's back a bit more and balanced instead of spread.
In other formations I use very similar tactics , just adjust accordingly
CASUAL
I don't know casual AI , but from what I have read it seems setting to never blitz and 100% pass defense does the best at stopping the run