You can certainly use a pair of small speakers like two π's and add a single subwoofer, crossed at 60Hz. You might position them where nulls from cancellation are counteracted by the sub or by boundary reinforcement. It depends on what you want, what you expect and to what extent you are willing to go.

I suggest maybe you might try a pair of two π towers first. The kits are inexpensive and perform very well. The cabinets are easy to build. That will give you something to work with, and is at least a good starting point. You may find that's plenty for you, and decide you don't need to go any further. Two π tower's aren't cornerhorns, but they are nice speakers that sound good in rooms your size. You can listen to them a while and decide if you think you'll want a sub later.