It's going to be set in our galaxy, Earth an important and wealthy planet being where humans came from but it's not the most wealthy because there are bigger planets with more resources. It's not going to be high space fantasy with FTL and robots and the like, more Sci-fi but a more gritty and dirty version. Technology is very advanced but hard to come by and the most powerful tech isn't hand held.
1. How about we have aliens but they're not as advanced as humans, one or two races that were discovered and are now treated as second class citizens by most and slaves by some.
2. Perhaps we can set it during a civil war between the central planetary government and a large number of outer planet rebels. Our crew will be neutral to begin with and simply be trying to make a profit from either side.
3. Keep in mind we're going to be a relatively small crew so a warship isn't very practical, though it could be interesting as we struggle to move it.