I use the rest depth chart to rest my top guys or low DUR guys in blowouts (something like a 5 run lead or deficit in the 5th or later, found in manager's settings)
I use the def replacement setting at 1 lead or more in the 9th (also found in manager's settings). Set your depth chart for the best possible defensive positioning. This could mean your SS shifts to 3B, your 3B shifts to RF, your RF shifts to 1B, and your 1B is benched (as an example). There is no offensive consideration given, you might be thinking of pinch hitting? If your depth chart for replacements is set correctly, your best defenders will come in.