First, of course, Focus on RUN. Your men won’t charge as aggressively, letting them stand their ground and move to the ball carrier. Linebackers don’t immediately start dropping back, watching for the run.
Next, position your men where the ball carrier’s going with your formation and shift. Learn to recognize the offensive formations, but also watch your opponent’s tendencies. The 4-3 and 3-4 formations are stronger run defenses than Prevent and even Nickel.
The 3-4 is slightly better than the 4-3 against outside runs.
With a four-man line (anything other than the 3-4 and Prevent), you can shift Over, Under, Tight, or Wide if you’re pretty sure you know his point of attack. Otherwise, stick with Normal shift.
BLITZ. Blitzing can put more men at the hole than the offense can handle. Outside blitzes can wreak havoc with Sweeps, and inside blitzes can destroy Draws, but don’t blitz up the middle if your opponent tends to call Traps.
COVERAGE. Zones are generally better against the run, unless the defense is in a “short yardage” or “goal line” set, where everyone is selling out on the run.
KEYS. Don’t stunt. Normal keys are best against misdirection plays, while Flow is better for standard runs. Keying a man is great if you key the correct man.