About the only time Reserves ever get used is if due to injury or foul trouble. Or in rare cases a complete blowout. If you select depth chart, I think that means he only chooses players from the depth chart, but the coach may move the positions around as he sees fit, only way I know to make sure that doesn't happen is to use Strictly follow Depth chart.
This is from what I understand, someone more experienced will probably be more educated.