While this is rather a pointless conversation -- as others have noted, if you don't like the default setting then the game lets you create any number of alternatives -- I enjoy the Charted Space setting. Whether I set a game/campaign there or not is up in the air, but then I enjoy both the universe and the game, and I'm quite happy to enthuse over one divorced from the other. I pour over and catalogue the established setting information, but how much of it gets used in an actual game is an unrelated matter.
I find the OTU setting very rich, personally; the key idea of no FTL communication independent from FTL travel means that the whole thing works as a pondering on how societies hold together (or fail to) across great distances. The three big human nations have different approaches to the task of keeping themselves meaningfully united in the face of distance and delays; the backstory of the Long Night provides the understanding that many worlds fear fragmentation of the larger social network as threatening to their prosperity or even survival. But no-one evolved to have an enduring social structure that spans parsecs of distance and months of silence -- so what to do?
The Imperium goes in for cosmopolitanism under an umbrella of feudalism, letting culture do as it will on a given planet but ruthlessly controlling the trade and politics between the worlds, with responsibility moving up a chain. And of course this system is itself a compromise between the Vilani "everything must be controlled so it's the same as it ever was" and the Terran "but I want to go there and do that."; the Vilani notion that anything not understood and controlled is a threat, the Terran notion that opportunity comes from change and innovation, and their mutual virtue of "let's expand to grasp it and profit from it." Plus, every notable demographic that isn't mainstream Imperial is itching to push the boundaries as much as they can get away with to assert some form of political independence. The Lancians and Luriani get their cultural regions to keep them happy in the face of potential mass defections from Imperial rigidity; the Vegans get their autonomous district because politics on the Solomani Rim made it useful to the Imperium. The Bwaps get it by working within the system so well that they're actually bucking the rules without anyone noticing (their multi-stellar Council of Creches, their history of getting the jump-2 drive) -- that's a tree for you, the roots dig in, after all... The Geonee and Suerrat and Darmine and Chanestin aren't allowed to have it because if any one of them achieves too much independence, the others will want it and there goes the empire. But they're all chafing.
The Solomani try to create a sense of a unifying *nation*, whatever a given Solomani perspective might mean by that. (The Imperium and the Solomani complain about the other's racism and corporate-noble dominance respectively, and they both have a very real point, but the real reason they don't like each other is simple -- one's an empire, the other's a nationalist movement. One will always consider the other the enemy).
The Zhodani go in for "social engineering" (taken to the extreme of "mental engineering"); trying to change human nature rather than being constrained by it.
All three approaches have their benefits and pitfalls. On a smaller scale, any interaction between worlds of various sizes and tech levels can explore more nuances to the theme. What's the conflict? What's the nature of this relationship and the implicit consequences for anything that upsets or challenges it? Whatever scale you operate on, the setting has it as part of a wider web of interdependence. How much you or your players focus on the ripples spreading out across that web is up to you/them, but there's always opportunity to have a disturbance cause knock-on effects and changing agendas elsewhere. After all, isn't that the real point of having a setting many times larger than a given campaign will likely involve? An implicit context to everything that allows any twists/shakeups/expansions/contractions to make sense logically. It might never come into play that the Aslan you stole a shipment from has now lost standing in the clan and a marriage has fallen through, meaning political changes on nearby worlds... but the possibility is inherently included.
The aliens also serve to explore the theme, of course. The gregarious but ever-fracturing Vargr who make changeability a virtue (given their nature, they only try half-heartedly to stop the splintering, more interested in finding the advantage in any change); the carefully ritualistic, implicitly antisocial Aslan with their single culture but no shared government (as The Deep and The Dark pointed out, the reverse-Imperium); the manipulative anarchy of the Hivers and their "every one for itself -- but timidly and clustered together" schtick and patronising altruism; the K'kree and Droyne with their inbuilt dependence on the social group; the former unable to integrate internationally unless they force their morality onto others, the latter quietly squatting amidst and between the other factions, too secure in themselves to care about empires.
As a final point, saying that the Imperium inherently doesn't work is hardly new to the setting, since one of the official timelines has it implode and fall apart due to its peoples' multiple conflicting ideas as to what it *actually is*.
Or a fully expanded system with multiple colonies.
