Just wondering if there is a difference to QB logic if I ran two the same plays but first play is designed 100% for my RWR and second play is designed for RWR(33%), LWR(33%) and FL (33%). Does the first play put my QB at disadvantage because he has to pass the ball to my RWR no matter what as opposed to having 3 options in that second play? Is that somehow factored in or it doesn't have any effect on succeeding the throw?

Those are initial values... the game does run through a progression and updates targeting based on multiple factors (endurance, traits, position on field, etc.)