Playing Heisman, I was having a huge problem with this. Never had a problem on past games when I always played on All American.
The problem happens not only with out routes but after any kind of cut. I find that if I try to throw the ball just as the player is making the cut, that is when the QB might throw it behind him instead. The only thing I've is that you have to wait a sufficient amount of time until after the receiver makes his break before you can throw it and safely lead the target. That is unfortunate of course because it means holding the ball longer and possibly running out of room.