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In the rare event that the defense drops back or adds extra defenders, simply Hot Route your best receiver and have him run a curl route he'll always be wide open due to always being against one of the backups from the other team. The defensive AI will never figure this out, and you can literally run this same play over and over again until you score whenever you have the ball. This will cause your best receiver to either be matched up against one of the worst defensive players from the other team or to be wide open outright on virtually every play. When on offense, run the Slants play from the five wide receiver Shotgun formation. Regardless of what team you're using, choose the Washington Redskins playbook and then put your best wide receiver at fifth on the wide receiver depth chart. Thanks to being able to use any playbook in the game on offense as well as the ability to line up any player at any position, you can easily use this to your advantage and move the ball virtually at will.
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