Normally what I do is pick my slowest, least TACKLE rating safety and use him to basically blow up the play. If you can just get your hands on the RB and slow him down somehow, your other good players will come in.
Dont worry about closing off lanes, most of the time YOUR the one supposed to be in the lane he will change to anyway. Just take a direct a route to the ball carrier as possible. If you get caught on a lineman or FB or what have you, dont switch right away. That twitch instinct will kick in and youll whiff.