From a "professional" point of view, this will make a difference, with some of the cheaper lens's that are out there. Many are set in the mount without any regard to the correct correlation of light bending. Think of astigmatism in the eye. The same thing. The better quality lens's such as those from Leica, Nikon, Cannon, and Schneider-Kruznach, to name the top 4 (in order) take that into consideration when the lens is assembled. With any of these you will not notice any difference no matter how you hold the camera.