When you're in orbit, it's the orbital plane, when you approach a planet, it's the ecliptic plane, when you're in the galaxy, it's the galactic plane, when two spacecraft meet, they're going to settle for one coordinate system as well. Point is, there is ALWAYS an Up defined. Otherwise you couldn't navigate properly.
And if you have a single spaceship, then Up is simply where the ceilings are. And nobody would design a spaceship with an interior where there is no recognizable up and down, because humans would go crazy. Every module of the ISS has a ceiling and a floor, despite zero gravity.