I’ve recently made the switch to a MacBook Pro running OSX. I also use an M-Audio USB Audiophile (http://www.m-audio.com/products/en_us/AudiophileUSB-main.html) which supports Mac right out of the box. However in applications like iTunes that do not allow you to select which device you would like to output to, if you use SPDIF there will be no audio. The Audiophile drivers for OSX do not provide the option to select an alternate interface from within Audio in System Prefs either.

There was very little documentation however the solution I found was to simply deselect the Analogue Output from the Audiophile config app.

The M-Audio site also advises the following;
The use of USB Audio Devices on the Right-Hand USB Port Is Not Recommended.

The 15″ MacBook Pro models have 1 USB port on the left side, and one USB port on the right side.
The 17″ MacBook Pro models have 2 USB ports on the left side, and one USB port on the right side.

Due to the current USB configuration of the MacBook Pro under OS X, use of USB audio devices is supported on the left-hand USB ports only (the port or ports next to the power adapter cable). Use of such devices on the right-hand USB port is not advised because it may cause audio interrupts and/or dropped samples. However, the use of an iLok on the right-hand port has been qualified and is fully supported.