Sadly or maybe not so sadly, there is no magic formula for what is going to sound best. The room itself, its size and shape, listening position, acoustic treatments, type of music and whether or not you intend to augment low frequency response with subwoofers or not all play into what will work the best for you. In general, the larger the room the more low frequency cone area you need to have for full bandwidth response. The louder you want to listen, the more low frequency cone area you want in general. In your room I would want something with a couple of 12" drivers for low frequency support so that almost certainly means at least a 3 way system if not 4 way. A pair of Legacy Focus SE for mains would likely work very well in your room. Not cheap but this is a full bandwidth solution with a very healthy dynamic range and by some reviewers among the very best available at any price. Worthy contender at the very least.
What type of speaker would sound better?
1. mid-tier 3 way with multiple lower quality drivers and parts OR
2. High end 2-way with premium crossover parts and speaker drivers.
Either one could be a stand mount, small tower, or anything in between.
For example you listen to a well recorded symphony in a 15 X 30 living room. You have 250w @ 8ohms. You start on a mid tier 3-way and then on a high end 2-way system, which do you think would sound better?