Well, today's been a pretty big day for Star Trek vs Star Wars noise. Nothing surprising, but it's a good opportunity to discuss what makes a setting compelling for games and fans.
I've run games in many universes - Star Wars most, but also Star Trek and some others such as Serenity/Firefly. The games I run do not use the official rules for these settings, because those rules suck.
Fundamentally, this makes the games I run more like fanfic than, say, playing KotOR. I've personally found that what seems to make a setting draw in a lot of long-term fanfic also makes it rich for people who want to play games in that setting - whether they are unofficial games like mine, or multi-million dollar computer RPGs.
With that in mind, let's take a quick look at popular settings, flash-in-the-pan settings, and how you might adjust your own designs to make them more... fanfic friendly? Let's say "enduring".
The settings of Star Wars and Star Trek are both good examples, because they appear similar at first glance and utterly different at second glance. So we can pull out both similarities and contrasting elements, and discuss why both are so enduring and popular.
Please note, we're not talking about specific canon elements. We're talking about the fundamental pieces of the setting, as might be used by fanfic writers, game designers, and idle teenagers everywhere.
Both Star Wars and Star Trek share a specific trait: their Space Opera roots. Both involve traveling to new and interesting places, but rarely alone or penniless: you usually have a group of hyper-competent friends, a kickass starship, cool powers, and/or a whole government pretty much blanket backing you. Similarly, you are restricted as to how you can behave, or you'll find your backing pulled or your powers turning against you.
This is pretty much the exact same setting as all of the old "adventurer archaeologist", "Private Eye noir", and "great white hunter" stories, and so on. I'm sure that in the days of ancient Rome, they had stories about the Roman legion's escapades in far-off lands that filled the same niche.
Obviously, this "backed exploration" allows for basically infinite expansion, and even if you choose to do something which doesn't involve a lot of exploration (such as Deep Space 9, where you're actually stationary), you still benefit from the fact that the universe has that kind of wide net already built right into it, and you can bring the exploration to you.
I suggest that this is the fundamental method to making your settings more enduring.
Take a look at other popular franchises: in Hogwarts, students explore more and more of their magical world backed by the support of their fellow students, teachers, and artifacts. In Naruto, ninja range far and wide to discover unusual (usually ninja-related) cultures and situations, and fight them. In Avatar, small groups of heroes hop on a giant flying monster and explore their complex, highly varied world. In Ranma 1/2 (don't laugh, it was basically the Naruto of its day), the main characters encounter thousands of crazy martial artists and there is a distinct feeling that there are an infinite number of ever more unlikely challenges out there, but you always have your (admittedly pretty useless) family to help.
Are there any popular settings which aren't built around this basic principle?
If you choose to build a setting using this approach, your main concern is how you spend your time. You have to hook into your audience enough that they begin to imagine other adventures right away. You can't let them watch a few episodes and then escape.
Because of this, you need to develop your primary backing and your competing exploration teams right away.
Your primary backing should be obvious. You're not just exploring new places. You're exploring new places with specific kinds of people at your side, specific interesting resources, specific restrictions.
If you're in Star Trek, you're exploring with a crew of trained professionals and a top-of-the-line starship, as well as plenty of magic technobabble. If you're in Star Wars, you're exploring in a dingy ship, maybe only one or two companions, but you can see the future and have a freaking light saber. In both cases, you are also bound: you can play fast and loose with the prime directive, but any actively evil captain will get their ass kicked by the Federation. Similarly, falling to the dark side is an ever-present threat that will rip the character out of the player's hands and leave them a villainous NPC.
So quickly demonstrate those details in the very first story. Make it clear the ship is funded by a benevolent super-government. Make it clear that you have psychic powers but they can make you crazy if you step out of line. You are adventuring. You have resources, and you have restrictions. Show them.
While creating your initial adventures, you'll also want to establish your co-adventurers, your competition. The entities and cultures you first encounter when reading/playing will be the ones that are assumed to be co-explorers anyway, so make them with that in mind.
As examples go, in Star Wars the competition is not the Sith, but the Empire. Later, criminal syndicates are the main competition. Wherever you go, there is a risk that they got there first, that they are entrenched, or that they will seek to steal it away from you.
In Star Trek, you have the Klingons - the first other explorer introduced, and still the most durable to the day. Until the Klingons, there were really no co-explorers. The Klingons were the first entities that A) could challenge the Federation to some extent, and B) were interested in doing so.
Of course, Star Trek tends to mint co-explorers for each series. Nothing wrong with that.
This kind of competition - another entity that is exploring and searching just like you - is critical for several reasons.
1) It serves as contrast. 90% of the time, the competition doesn't have the same behavioral restrictions that you do. So you are competing 'at a handicap'. Except... it also gives the writers a chance to show why operating with your restrictions is beneficial.
2) It serves as pressure. Knowing that there is someone else out there - an evil version of you - means you can't just freely waltz around. Sometimes, you'll enter a contested zone. Sometimes, you'll need to fight tooth and nail. Without competition, each adventure is simply you tromping on the locals, or the locals tromping on you.
Are there other factors that are important?
Sure. Design sense, popularity, music, character design... lots of other things can help or hurt you. But the differences between the popular settings we've mentioned show that none of these things has a "best" approach.
The only thing that seems to have a clear "best" approach is the fundamental way you base your setting around exploring with backing, restrictions, and competition.