Reggie Wayne is a receiver I do not think gets enough credit. People look at his quarterback and assume his job must be easy. In reality, he does everything well. Santonio Holmes' game reminds me a lot of Wayne's. There is not much Santonio does poorly.
Holmes' teammate Braylon Edwards is known as a vertical threat. That is because it is where he does his most damage. Holmes' game is much more diverse, but he is fast enough to burn defenders deep. He does a lot more well, though. He utilizes double moves to beat his men. He is capable of cutting under safeties deep because of his route running skill.
His excellent route running also makes him a fantastic option underneath. So does his uncanny body control and knowledge of where the sideline is. Nobody in the league is better at making a tip toe grab to stay just in bounds.
Holmes is a heady receiver as well. Take his touchdown in the AFC Championship Game. He read the coverage after Ike Taylor fell down and broke off his route because he realized the Steelers had no help deep. He threw up his arm to signal this to his quarterback. It led to a touchdown. It is difficult to teach that kind of football intellect. His hands are also usually good despite an uncharacteristic 5 drops during the 2010 season.