Like... we can only really set to defend vs. the run or the pass. We can't say "Oh, but we know, that this guy always runs to the weak side" or "this team is fully committed to outside runs".

So if I only ran inside runs, would the opponent's defense react to it and shore up the inside on run keys, or is it just tough luck?

Same with passes. Say my playbook was 40% inside runs and 60% long passes, would they actually defend deeper naturally, after having only seen long passes for a half?

Just a hunch, but I think if you had a diversified enough playbook (say, 20 of the runs and 20 of the passes) to avoid the same play being called enough times to trigger the penalty for that specific offensive play call, that you'd see no adjustment. I've never seen language indicating that the game keys to inside vs. outside runs or long/medium/short zone for passing.