As for professional hitters, when they sit on a certain pitch they adjust their timing. They don't physically look at the ball and guess what the pitch is when they see it traveling through the air.
If you sit on a changeup, you adjust your timing to swing a fraction later than you would fastball. So it doesn't matter what the ball looks like coming out of Santana's hand, they just have to follow it and swing based on their best estimate of the changeup's time of flight.
In other words, they know what they are swinging for before the pitch is thrown. There should be no guessing like your post implies.
Last outing, he was beating everyone on changeups low and away. I just think we can be successful if we look for it late in counts.