depends on what you're trying to do and how the software for the sound card handles things. In my experience (which may differ greatly from yours), for music i manually set the sound card to 2.0 only mode, and disabled all enhancements/extras in the software. Then i'd play music, preferably using wasapi or asio to ensure the sound card driver isnt screwing with anything in the signal path.
for movies, it can go either way. the best result ive had is going out to a multichannel receiver and using the downmixer within the receiver to get things back to stereo. This gave me the best result and i have yet to witness anything as nice from a sound card. Granted, it has been a LONG time since I bothered doing that anyways. For gaming i did a similar thing. I set my sound card to 7.1. i set the sound card to use dolby digital live because i had an optical connection and needed the signal compressed to dolby digital (or dts, if you have dts ultra-pc) in order for it to get to the receiver fully. If you use hdmi to a receiver, then just set the sound card to multichannel and skip the processing step.
now, if you arent using a receiver and are going right from the sound card, i think you only have a couple options. 1) do nothing, set it to 5.1 or 7.1, let the sound card do whatever it wants. 2) set the sound card to "virtual surround sound" and calibrate it. You should only be able to do this if the sound card is in 5.1 or 7.1 mode. The real question is, when you play 2.0 music, does it sound different if the sound card is set to 2.0 vs 5.1+virtual surround?
in my experience, music sounds best in 2.0 with no other processing applied, so i kept manually changing between the two options.