Right now I go with familiarity only, but can't say I'd waste time scouting an unfamiliar play that gives up say, 15 yards per average for example.

Tho I am aware the scenarios I'm discussing here for examples sake are very broad, always more variables and complexities involved

You might. Or that unfamiliar play may end up with your QB throwing a pick six. Familiarity is more important than how many yards a team gives up. Maybe the other teams they were playing were familiar with the defensive set.