Even though i havent been approved to the site as of yet im definetely interested in a 40K RP. If your not going to use a system style then any setting will work well. Crusade can easily be done but a strong Lord character would need to be NPCed so as to keep the players from killing each other openly and to give some kind of direction. Rogue Trader (my personal fav) would also work best with an NPC captain but not necessary. Only war would need to be set up as a special ops style group so that a wierd mix of players makes sense. Dark Heresy would be easiest on the GM due to its low powered characters. Deathwatch would be the hardest IMHO. Ive run one in RL and everyone wants to play a different chapter or one they made up themselves. Also if you get over 10 players it wouldnt make sense.
Just my 2cents there. Hope to get approved soon and that this idea sees light.