Fatigue settings during a game have a big impact on injuries by keeping players fresh and distributing snaps.
The default settings are, like most default things, awful. Your RBs are going to get 400 carries a year. Dropping these down to 40-45 and keeping multiple RBs on hand allows you to go to a committee approach while letting your #1 do the most damage.
If you can handle the override settings, keep a dedicated 3rd down back on the bottom of the depth chart to sub in to catch passes. Let him get 40 carries and 40 catches over the course of the season and watch him get 400-500 yards receiving and 4-6 TDs without ever running for 100 yards in a game.