There are so few off days that, if you run a 4 man rotation, you have to stay on top of your pitchers' fatigue. You will likely have to have a spot-starter every 2 or 3 times around the rotation.
I haven't noticed it, but some say pitchers take longer to return from fatigue at the end of the year if they've consistently pitched the day they return to 100% rather than having a day at 100% to rest.