On the Mound Right down the middle of the plate is the worst spot for a pitch. Even if you think a batter might be looking for a pitch away or in tight, he can usually adjust to a pitch down the middle and drive it. Work the corners and the edges of the strike zone. The better control your pitcher has, the more you can target the very edges of the zone. You don't always have to throw strikes.
Nothing can wipe out a lead faster than a tired pitcher.
Keep an eye on your pitcher's energy level and bring in a reliever at the first signs of fatigue. Check out your pitcher's ratings on his individual pitches. If it's a tie game and your opponent has a man on first and no outs, access the infielder positioning menu and prepare for the bunt. Know the speed of the opposing batter. This will help you decide whether or not you need to risk an aggressive throw to get him out at first.