I run mine in stereo, though mono may work better. I don't have nearly as much free time to play with set-up as I would like. For my pressent room configuration my guess is that mono will work better. Also the crossover point would help dictate this.
Two smaller subs can do more work than one larger sub. mine is set up with three 8" woofers for each side. There is no problem with getting lots of bass. A room of 3,500 cu/ft is fairly large. Finding a high output sub that is also detailed can be difficult. There is a guy selling a pair of NHT Sub2i's right now. I know that these are VERY high output and would fill your room. It is just a question as to personal taste though.