You would likely start from the center of your galaxy, then pick a culturally relevant star near the outskirts, in our case Sol, and call that, well, something (Solbound?) Then work your right angles from there. You could pick other cultural stars in the other directions too.
Most galaxies are pretty flat, so you’d probably have to reference a conveniently positioned other galaxy for your up and down.
Aeon Flux was a weird one. Had some cool stuff going on, but the execution was shoddy