This can easily be done with two controllers. When controller two is on offense, pick a pass play where one receiver is alone on either side of the field. The defense can pick any play, but make sure you pick the same one to get an interception with the same player each time.
Once the play starts, with controller two pass to the receiver who is alone. With controller two again, press to switch to that receiver and then run away from where the ball is going to land. The defensive player should intercept the pass.
When you intercept the pass, you can probably run for a touchdown and get Pick 6! here as well. If you can't get it on your first try, you will have at least two more chances that game.