There is a debate in Eve Online circles about the role of small, independent corporations in null-sec. To wit, there really isn't one. Null-sec has come to be dominated by large empires. To move into null-sec, a small corporation must sacrifice their independence, and generally bow down to one of the major powers.
I think this issue is not specific to Eve Online. Almost every sandbox game ends up with a similar problem. People want to be out on the frontier, to stake a claim, and watch that claim grow. It's very much the myth of the American West. But inevitably, these games run out of frontier.
But Eve has hundreds of star systems. At first glance, it seems that surely a frontier can still exist. The problem in Eve is that it is too easy for an empire to project force anywhere in its claimed space. If at any given time, the empire can bring its entire force to bear without repercussions, then warfare essentially becomes about who is larger. And the empire will always win that battle against a small corporation.
Let's say you have a large null-sec empire. A small corporation takes one star on the border. What happens? The empire drops its entire fleet on that star. There is generally no real downside to doing that.
But imagine there was a downside. Let's say it takes two weeks of real-time travel to get from the heart of an empire to its border. Now, the empire cannot send the entire fleet, because if another empire invades, it would take the fleet over a month to get back. Instead the empire has to send just enough ships to deal with the small corp. And the resulting battle might actually be won by the smaller corp, if the empire miscalculates.
The empire has to be able to be stretched "too thin" for smaller corporations to be able to exist alongside it. But so long as it is easy to project force, as long as distance does not really matter, the empire cannot be stretched too thin.
To be honest, I don't think this problem can be solved without significant travel time that lasts longer than a single play session. Significant travel time introduces logistics, supply lines and military strategy, as opposed to just military tactics. But significant travel time is highly inconvenient. I really doubt that anyone really wants to take two weeks or more to reach their destination.
But without significant travel time, it becomes a numbers game, and then a game of covert actions to influence that numbers game.
Frontiers cannot exist without meaningful distance. If you want your game to have a frontier, the price is the inconvenience of distance. And I don't think that players will accept that price.