Also maybe check out https://godotforums.org/discussion/23575/what-to-do-with-leftover-rpg-stuff where I muse over twin-stick combat with an RPG-esque team of characters.
Setting?
So, first of all, the main attraction to me is the open-worldness, not necessarily being in space, per se. Let's think through some settings.
Galactic Space - This would be the normal setting for these sorts of games, you visit various star systems, each with their own planets and things to do. The trick here is that this kind of game universe is very big, and you need to either come up with a way to fill it or avoid it.
I like 3DR's approach that you only visit space stations and trading posts. There's a modern idea in Futurism that space colonization will not be about living on planets, but building space stations to live in. Earth is incredibly unique, we will probably never find a truly "Earth-like" planet, and when you really crunch the numbers, it's much more plausible to build swarms of space cities than it is to terraform a planet like Mars or Venus. Isaac Arthur had a great quote in one of his talks, that basically, future humans will think of planets the way we think of the caves that our ancestors lived in. We will not cross the stars looking for new caves to live in, but for houses to build.
For mor on this idea, check out SFIA-Oneil Cylinders SFIA-Life on Oneil Cylinders and SFIA-Nomadic Civilizations
That said, I also like Interstellaria and Star Trek Online's approach of having specific points of interest you can visit. For example, you might haul up to a planet and see a list of spots you can visit, like Big City, Ancient Ruins, Dangerous Jungle, Mysterious Crash Site. However, I think it works for those games because they are fairly story-driven/mission-driven and I don't know how well it would work for a more open-ended game. It would be cool if points of interest were randomly generated, as that would open up more possibilities for the size of the universe.
System Space - Instead of jumping from star to star, everything takes place in a single star system. This would save me from having to deal with FTL transit. Although I can say warp, hyperspace, wormhole, etc, I'd still have to come up with a game mechanic for how the player activates their warp drive and actually switches between normal speed and super speed.
It would also allow me to focus more on the single star system and fill it with a more life-like level of activity. Instead of 5 or 6 points of interest on a single planet, it could have dozens. If we go by the houses-over-caves approach, you'd probably have swarms of space stations you could visit that cluster around planets or asteroid fields to gather materials.
Solar System - A variation on the previous topic, the game could be set in our Solar System specifically. Earth, Venus, Mars and the bunch. This gives me more to work with since there's a lot of information and ideas about what our planets are like, how we would colonize or utilize them. I've even written a game in this setting before, the flash game Blazing Void (although it is not open world).
-Tangent-
From my previous research, I actually think that Saturn would start to eclipse Earth as the most important or most powerful place in the solar system. It's an attractive colonization target. Saturn has the most Earth-like gravity of any other planet, 1.07G to Venus' .904. Unlike Mars or Venus, Saturn has a native magnetosphere that can protect people from harmful Solar radiation, and unlike Jupiter, it's not strong enough to microwave you or disrupt electronics as you get close. There are also resources there. Saturn itself has Helium-3, a fusion fuel that many say will be the black gold of the future. There are plenty of mini-moons and space junk around Saturn which could be mined for minerals, and also water. The big moon Titan has various interesting qualities, and could be especially interesting as a space port or shipyard, since the low gravity and thick atmosphere allows you to more easily land and take off.
And you might be thinking, "but there's no ground..." True, but on any planet, you're going to have to do a lot of building to make it habitable, so it's not that much more of a challenge to build our own floors while we're at it. There's a lot of talk about building floating habitats on Venus, and I think a similar system would work on Saturn. Saturn is very different though. Venus' CO2 atmosphere is way thicker than Earth's NitrOx atmosphere so a balloon filled with NitrOx would float on Venus the way Helium floats on Earth. But, Saturn's atmosphere is made of Hydrogen, and there's nothing lighter than Hydrogen. However, Saturn's "surface" temperature is really really cold, -140C/-220F, so you might be able to do like a hot-air balloon to stay buoyant. At the same time, Saturn's atmosphere gets thicker, but warmer as you go down, eventually becoming liquid Hydrogen and then metallic Hydrogen. There might be some sort of goldilox layer on Saturn where the pressure and temperature are not too bad, but to my knowledge, this isn't something they've done a whole lot of science to yet.
-End Tangent-
Anyways, I could totally see a political rivalry between Earth and Saturn, or between the Outer and Inner planets as source of conflict and motivation for a Solar System setting game.
Jovian System - To go a little smaller scale than Solar System, gas giants tend to be like miniature star systems. Even though I've just explained why Saturn is OP, Jupiter (AKA the Jovian system) strikes me as a more interesting system for a sci-fi game setting.
The main thing you might not know about Jupiter is that it is constantly spewing a massive blast of electro-magnetic radiation that begins to microwave you as you get close. (which is a rad effect for the Thunder God's planet) You can actually hear "Jupiter's Howl" from Earth on AM radio stations. I think this would be an interesting gate-keeping mechanic for a video game, the more radiation resistance you buy, the closer you can get to the action.
Jupiter itself has resources like Helium-3 and other useful gasses, but the high gravity and radiation would prevent you from just driving up to it and scooping up the goods. I imagine instead big ships basically bombing the planet with explosives or lasers and collecting gasses as they blast up into the stratosphere. Jupiter also has the 4 Galilean Moons, which might serve as habitats, shipyards and such, dozens of mini-moons which could be mined, and the "Greeks" and "Trojans" lagrange point asteroid fields.
Check out SFIA-Colonizing Jupiter for some more ideas.
I imagine the Jovian System colonies as a rough, almost dystopian place. Asteroid miners were humankind's first trillionaires, and the Saturn colony has been hugely successful. Now, space industry mega corporations are trying to exploit Jupiter. People who know what's up aren't interested. The corporations recruit from the downtrodden masses and criminals from Earth and the inner planets, promising riches, handing out a free ship and new identity in exchange for contracts to work in the Jovian system.
To Be Continued...