Eh hem!...Subwoofers... What do ya know?

Does the direction of either the mains’  midbass driver or the sub make any difference?
Like if I point my mains away from a bass null would that help negate it?

No, its the physical position of the sub that dictates where the standing waves end up . Put the sub on your listening chair , now go around the room and find where the bass is loudest. Now put your sub there. The end. Leave your mains off during this. Makes it easier. And less violently loud while you figure it out.

@davekayc what about 2 way bookshelf speakers? Same?

Theres no magic to placing your mains . Rule of thumb is placing at eye height and the distance between them is how far either is from your head . 60 degree triangle . I’m not quite sure what you are asking but the soundstage is the biggest part . Make sure the set up is in the center of a wall . Its all about YOUR ears . Everyones ears are different. All anyone can recommend is better math.  Other wise ear buds wouldnt have adapters for different shape ears. Poor symmetry   makes premium equipment sound midfi . We were only talking about subs and the various methods of use. 

@davekayc  I'm fighting a bass null at the sitting position so I wondered about, having the mains spread further apart but toed in at a steeper angle to limit low frequency waves going straight at the wall and being reflected back. Basically having the very toed on speakers sending low frequency waves at the rear wall at a steep angle vs nearly head on to negate the null.

Unless I move at least 38% of the way into the room (better at 50%) I sit in a mid bass null. I always thought the speakers were bass shy but the sub I've been messing with has the same issue so its clearly the room and not speakers. If I mive 3ft to the right of the couch/sitting position which puts me in front of the hallway entrance the sub is delivering THUNDER. Move back to the sitting position and its a little warmer at best.