I have both the on-wall (with a Denon 3313) and in wall (with a Denon 1713) in my master and den respectively. I like them both a lot without really favoring either. In fact I like them so much I wish I had put them in my living room too (just for the looks) instead of a much bigger M80 v3 (with a Denon 4520) system I have which is too much for the space.
My Den does not have a sub and I don't really miss it. My master has a E350 which works well as it is part of a full 5.1 system. If you are using the M22's for more than casual listening I would recommend a sub too.
1 M80,vp180,qs8,aim7,EP500,Denon4520,Rotel RMB-1095