What is Shadowrun? When I've been asked that question I usually embark on a long description of the game, the setting, and the fluff. This works for new players, and helps people understand what they are getting into, but it's limiting in and of itself. Let me give you an example.
I happen to frequent a local game store, as I like to shop local, and as chance would have it one of the fluff writers for Shadowrun 5th Edition also frequents the store. We got to talking, and she took me to task after I stated that Shadowrun was based in Seattle. Her point being that, as she wrote for Catalyst, she knew that the plot wasn't going to be Seattle-centric, and therefore I was wrong to state that Shadowrun was based in Seattle. This got me to thinking, first that it's silly for a person who is a representative of a company, however, peripherally, to be arguing with that same company's customers, and second, what exactly is meant by a setting, or really, a system at all?
Let's look at system first. There are two main game systems. The first, is a threshold based system. This is the D20 system, in a nutshell. You have a target, if you roll over it, you succeed, under it, you fail. You also have a success based system. This, is Shadowrun. You have a pool of dice, and if enough dice succeed you pass, if they don't you fail. If you want to describe Shadowrun in minimalist terms, you would describe it as a success based D6 system. That's it. There's no trappings of settings, or fluff, it's simply the system that is used, and the type of dice rolled.
Now, let's talk setting. Setting is where the game's fluff takes place. This is often confused as being where the game itself takes place, but once you remove the fluff, you're often left with very little in terms of setting. In Shadowrun 3rd, and 4th, edition the game's setting was Seattle. In my mind, this continues into 5th Edition as well. Regardless of the official cannon. Why does this matter? Let me explain.
For years now, I've wanted to run a role-playing game set in Prohibition. That is, 1920's era, New York City. In order to run such a game, I went looking for a set of rules who's fluff meshed with the setting I wanted to run. What I should have done, and this comes back to the discussion in the game store rather neatly, was adapt a game system, to fit the setting I wanted to play. What's to prevent me from taking the D6 based success system of Shadowrun 5th Edition, and dropping it into a 1920's era setting? Nothing. That's the great thing about viewing a game as a system, and not as a setting.
But, let's keep it a little closer to home. I have a group of players, and they've never been to Seattle. Tacoma means nothing to them, nor does Redmond, Bellevue, or Lake Washington. The setting, as it's presented, is meaningless. Why use it? I know we get attached to a setting, and we feel that we have to do whatever it is that the designer wants us to use, but why not set a campaign in your own home town? Have your players meet Mr. Johnson in your favorite local watering hole, and meet up for after-the-Run dinner at your favorite greasy-spoon.
Remember, it's your game, and your players game, if they want to keep the setting in Seattle, great. If not, great. Do what you want with the system, regardless of the setting.