One of the things I like doing with an established setting is to focus on a particular aspect of the societies and norms inherent to it and either highlight or twist it slightly. It doesn’t have to be anything huge, even small tweaks can actually have significant effects on how a game feels and plays without changing the rules.
One example I’d like to use is my recently concluded Legend of the Five Rings campaign, “Never a Dull Blade.” In this game, I focused on the Lion Clan in exclusion to all the other Clans. While some people feel that the default for an L5R game would be one that uses multiple Clans in an Emerald Magistrate game, I figured that focusing on domestic issues rather than the usual Empire-scale threats would make for a more interesting game. Thankfully my players found the game lot’s of fun even if they weren’t allowed to pick from the rest of Rokugan’s numerous (and admittedly flavorful) Clans.
A more recent example that involves a bigger tweak would be the Mage: the Awakening campaign I’m currently running, “Endangered Species.” In this game, Japanese have stopped Awakening, leaving the Japanese Awakened community in a state of crisis, and realizing that they were dying off. Without fresh blood, the issues become one of mortality, succession, ambition, paranoia and fear of death in an aging population. As the pressure mounts, I figure that many more mages will start turning to more desperate measures to survive.
The important thing to remember is that even old favorites can get tiresome if you play it enough times. My gaming group has been playing exalted for years now, and it’s no surprise that while they’re enthusiastic about playing, the GMs are starting to show some measure of creative wear and tear. After a while, there has to be something more to it. My solution was to add a twist where the characters were the first Solars to return, in a setting where the powers that be didn’t decide to kill them outright but observe what they would do now that they’ve returned (without the memories of their twisted and corrupt past lives.)
Being able to put a personal spin on game is a valid method of making the game yours. People might talk about Forgotten Realms or Ravenloft and Eberron, but you and your players will definitely have your own take on it, one that has improved on what was existing and taken it to places that are yours alone.