Hi there,
I own and use a Xonar D2x myself since it came out, best sound card I have ever owned. Instead of using the drivers ASUS provide, I use the UNi Xonar drivers since they use less memory and have a bit less latency.
As to speakers and headphones, the better the speakers or headphone the more you will be able to notice, given that you are not hearing impaired.
I would say the difference is big between an on-board card and a proper sound card, especially if you know what to listen for and the difference will be very clear of you A/B test the equipment with less than a couple of seconds when switching between them, as sound memory doesn't last very long, at least not for me.