Speakers + room for me. I have a loft that is medium size but it opens to a stairwell on the left side. That means the left speaker is separated by the stairwell with a half wall while the right is adjacent to a typical 9' high wall. Not all speakers like this configuration but it's what I have. Given that my open baffle speakers really shine in this room with only minimal corner treatment.
In summary: 1) sort out the room for the best listening position, 2) choose speakers that work well in the room, 3) adjust any treatment to account for room issues, 4) build the front-end that makes the whole system work.