Basic 4-4-2 has always been my preferred formation. Only very rarely have I altered it. At the start of each season, my first priority is to get my ML / MC / MR's as near as possible to scouts. Having 4 good quality players across the middle, and with a settled formation, seems to work well. I do however try to get ML's & MR's with the additional position of AML / AMR, just in case I ever need to push them forward to support the strikers. (I never use arrows).
In the lower levels, I used to keep enough players in the squad for two separate teams (League & Cup), but as I've got to higher levels, the players don't seem to play as well, if I keep changing them around. So its now a case of first XI plays all the matches, if they are fit enough.