I would say optimize for the middle since it seems a lot of the other settings seem to be done that way. I'm playing small right now just to get the hang of the changes but will be likely be playing more mediums later.
I'm pretty much of the same mind as stein220, who I quoted above. I have played most of my games on Small Maps, with an occasional game on a Medium Map. One reason I play the Small Maps now, is to play as many games as I can, in the time available, so as to get the best feel for the game that I can get, in the short run. Over the longer run, I expect that I will probably end up playing most of my games on Medium Size Maps.
Two Qualifications: I routinely play against one LESS opponent, than the default settings suggest, on both map sizes. I believe this allows me to play a slightly easier game. Also, it helps (a little) to "improve" the feeling of the first two X'es (eXplore and eXpand) in this "quasi-4X" game that you have created. Otherwise the first two X'es are under-represented.
Secondly, as I have a smaller, older, weaker PC at present, I think a Large Map would be too taxing (too slow) for my current configuration. As far as that goes, I am not sure that I would ever really enjoy playing on a Large Map. Like SciFi1950 suggests, the hard-core players, among the Beta Testers, may tend to play the largest possible maps; but the potenially larger, future audience for your game (of more casual players) may tend in the direction of Medium (or Small) Maps.
So, Optimize for the Medium Maps.