I have been more attracted to SF space colonization concepts that are a lot more decentralized. While the O'Neill type colony is exciting, it does require a lot more centralized authority just to keep things running and stable.

I like the kind of cultures that usually are depicted as "Belters." People with individual homesteads on asteroids or scattered on the Moon or elsewhere. Would require a certain class of technology, the Earth equivalent of generating your own power at home instead of using a central power plant.

The advantage to this is that once such technology is developed, colonization becomes a LOT cheaper than giant colonies.

In the realm of biological engineering, a method that would allow people to live their lives and reproduce normally in free fall would help this immensely, removing the need to "spin" structures or live in gravity wells. Unlike more complete adaptations to space (no breathing, etc.) I think this might be near-term feasible. Imagine what you could do with the volume of an asteroid (inflatables might have radiation issues). Being able to return to a gravity field is nice, but not essential.