I view this setting as fairly "typical". If you've played any other sort of D&D this setting is easy to get into. It does not require much from a player or DM other than some different rules for the entire domain/blooded actions. It does not require the players to play any differently or the DM to run things in any different sort of manner. If they had played Greyhawk or Forgotten Realms before coming to Birthright they would not have to alter their play at all.
This is very similar to Birthright. The players can play it and the DM can run it much the same as any "typical" setting. The only slight difference is the scale of character level and their abilities and the lethality of the setting that can take some getting used to. When the Dark Sun setting came out it changed the perceptions of character ability and danger, but ultimately it can easily be run as any other setting without diluting the setting. It is more about getting used to the setting as opposed to requiring anything special from the players or DM.
Here we start to diverge from the "typical" setting. Ravenloft is designed to be a "horror" setting. And this requires more from a DM than the "typical" setting. If a DM were to run Ravenloft as they would any other setting the goal of Ravenloft is lost. The setting requires more from a DM than other settings. For myself, I know I can not run Ravenloft effectively. I am not good at subtle hints of danger or a slow build up of fear and terror until it reaches an explosive climax. Therefore, I would be a terrible DM for a game in the Ravenloft setting. Ravenloft requires a DM that can bring these skills to the table. To do otherwise negates the goals of the setting. Ravenloft requires a skilled DM.
Can you think of any other settings that require more from the players or DM then the "typical" setting?