Given your budget, it may be worth thinking about the separate amp / receiver and speakers route rather than PC speakers. Also consider that most music is mastered for stereo speakers and, for music at least, you might do better from a pair or stereo bookshelf speakers. I'm not that up to date on PC and hi-fi speakers at the moment so maybe someone else can chip in?
Ultimately, this is going to be about balancing your budget to what suits you. I'll recommend a range of soundcards and speakers so you have a few things to consider.
If you're spending a fair bit on headphones, I would suggest trying them on, if not getting a full demo. I've got rid of quite a few pairs because I found them uncomfortable, even great sounding headphones. That's one think I really like about the Medusas and the main reason I sometimes still use them - the comfort.
Given that you're using Medusas I assume you're happy with open headphones? (Edit: I've indicated where they're closed - others are open) Here's a quick shortlist of Headphones you might consider:
Goldring DR150+
Goldring NS1000 (closed with active noise reduction - great for pc fan noise but requires AAA battery)
Sennheiser HD555 +
Sennheiser HD595 +
Sennheiser HD580 * (discontinued but you might be able to find it)
Sennheiser HD600 *
Sennheiser HD650 *
Audio Technica ATH-AD700 (reputation for having excellent soundstage, detail and comfort)
JVC HA-RX700 (closed)
JVC HA-RX900 (semi-closed)
Note: + benefits significantly from dedicated headphone amp; * absolutely requires dedicated headphone amp to get the best from them. I've colour coded them so that Yellow is stuff I've owned or had an extended home trial. White is stuff I've tried briefly. Red is stuff I'm recommending on reputation / reviews alone.
All of the above are headphones rather than headsets, but you can use a clip-on or desktop mike. Unfortunately there really aren't that many good headsets with a microphone.
Soundcard wise, I would be happy to recommend any out of the Xonar D1, DX, D2 or D2X. Bear in mind the note about headphone amps: The Xonar Essence STX has a fairly good one built in. It doesn't have the analogue connections for surround of the other Xonars so your 5.1 speakers or amp would need to be digital.