Seems to me that the M60/500 combo would be perfect for what you're describing as your room and listening habits. While the M22's would sound terrific, you indicted that you like to listen loudly. You could strain the M22ti's limits if you try pushing them too much in that sized room. I believe you'd give out before the M60's though.
Regarding the sub. A really great sub makes a WORLD of difference, in both music and movie enjoyment. I've not heard the EP500 personally, but it's gotten numerous rave reviews. If it's price is a bit steep for your tastes, I'd highly recommend the Hsu VTF-3. I have heard that one, and it's astounding. (Though I believe there have been some EP500 vs. VTF-3 listening comparisons and the EP500 has come out the winner - of course at nearly twice the price though)
I guess my long winded point is, don't skimp on the sub. You'll regret it.
