I don't see why not. I had my system hooked to my 32" tv on the wall next to me and my 24" monitor for a while and I had my game running on the monitor while I had winamp up on the tv keeping track of my music. Only thing about that setup is every time I wanted to change the song, I had to alt-tab out of my game. So, you should be able to. Open Media Player/VLC whatever you use on the side screen. Best way to do this is to extend the desktop in the resolution manager built into windows. Right click the home screen and hit resolution.
P.s: You should be able to do it with one card depending on what you have