Going to weigh in here and try to lend some outside perspective, since all of you guys make valid points, but it's hard to see the forest for the trees sometimes.
I've been familiar with the Shadowrun settings for a good while, but have only really had the opportunity to play regularly recently. However, I first played in 2nd Edition, so that's where that is. From what I've seen, certain things change while others must necessarily stay if not the same then at least similar enough to be recognizable.
The technology from 2E to 4E(which I am currently playing) has changed a bit, gotten more advanced, as it rightly should, since it reflects the change from clunky wired 80s tech to more neo-modern wireless stuff. Likewise, the plots, metaplots, schemes, conspiracies, and a ton of the people involved have shifted, changed, evolved, etc to reflect that life is not static. It moves. Constantly.
Now, the rules can change, the corporations and plots can shift, even the atmosphere can be altered a fair bit, but certain themes that make the setting what it is have to remain semi-constant. If they don't, the system ceases to be Shadowrun. Perhaps there is room for sub-settings, aka different locations, sprawls and whatnot that may have a very different feel to the main core game, sort of like how there's core D&D, and then there's the various campaign settings(Eberron, Forgotten Realms, etc). Just look at the difference between a game set in Seattle with a lot of cloak and dagger stuff, and one set in Bogota, where heavy armour and excessive ammo may actually be a good thing.
Through all that though, what remains constant is that corporations and nations are self-serving and monolithic entities, people everywhere get manipulated by other people, conspiracies are in fact common(just not commonly known perhaps), and society in general lives in a fairly gritty dystopian world, where there IS light and shining beacons of hope(depending who you ask), but the larger the beacon, the larger the shadow it casts. Shadowrun IS a dark, dystopian setting. Yes, it shares certain factors with other ones(you could run a Shadowrun-Mad-Max crossover fairly easily for instance), but it is it's own animal, and to change the nature of the beast is to fundamentally change the beast.
So, after that mechanical rant, here's the final point I think most people have missed so far, one that is purely in-game. Life has changed a lot in 20 years. It's changed more in 50 years. However, certain things haven't. Even in the 50s, 60s, 70s, etc, companies and corporations tried to get more power. It happened with Reagan, it happened with Clinton, and it's happening under Obama(using generic American examples as a constant, I'm Canadian). Likewise, technology progresses on, comforts and interests and music trends change, but people generally stay the same.
The first settings was in the 2050s, and it was established to be a dark, gritty, dystopian, "high-tech, low-life" setting. FASA designed it that way. Through subsequent editions, smaller things changed, but the world atmosphere largely remained the same, as no matter the circumstances, where there is money to be had doing illegal things for powerful players, there are people willing to do those things discreetly. In game-time, the difference between the first and 5th editions is about 20 years, give or take a few. So the difference in world view, atmosphere, etc would be about the difference between the 90s and now. Not actually that big of a difference, overall.
Also, final final point. While there is a dichotomy between Transhumanism and Dystopian cyberpunk influences, the two can coexist, in small doses. Someone earlier mentioned the Horizon/EVO example, which is perfect. The megacorps march towards what they see as a utopian world for their citizens, and the people who belong to the corps/want to belong see it as perfect beauty and harmony. However, a LOT of people don't want anything to do with that, and as such it's a relatively small and isolated cultures. Megacorps aren;t really isolated, but consider that only a couple of the Big 10 right now are really experimenting with these concepts, and at most they probably have a few hundred thousand employees. Not all that much compared to a world population of probably about 8 billion.
