Please note that the RME Babyface is a USB device, therefore it matters where you connect is with respect to the Virus (and this goes for any other USB audio interface). Other then that, if you succeed in giving the Virus the bandwidth it needs over USB, digital audio is digital audio, the connector type doesn't make it sound different. The differences are that you can send automation from your DAW over USB, as well as the fact that the DAW is able to compensate accurately for the delay of the VC plugin, and if I understand correctly from what I read in the forum, only out1 L/R are implemented through S/PDIF (although the standard supports more than just 2 channels).