If you use a 40 man roster before you play/sim spring training then the computer will choose who they feel are the best 25 guys on the team and you will see lineups/rotations way out of whack.
I would suggest using a 25 man roster, sim spring training, then add the rest of the 15 guys to each roster before you start the regular season. This will keep rotations/lineups intact. This would especially be beneficial if you are using 30 team control.
I manually injure players who are hurt in real life. I do add them to the 40 man unless they are out for the year. Also, I would suggest turning CPU trades to OFF. You can control trades so if something happens in real life you could just input in the game manually.