It takes time to establish a decent 22. AT least a few seasons to really nail it. You should end up with a favouring 11, that can be easily transformed mid-match to numerous formations using only a couple of subs. I always try to leave one sub in case of injury - which is all too common in this game.

I try to give all subs and reserves a game, even if it's only to give them a run out in the second half of a CL group game when I'm 2-3 goals up. Cycle the subs whenever possible. Use your best 11 for vital games.