The group I game with most of the time runs a Forgotten Realms campaign setting. We have played it in 2.0, 3.0, 3.5 and now use Pathfinder. There is very little change that we have to make. For 90-95% of it we just use the Pathfinder rules as is. We simply remade our characters for each edition as needed and custom FR specific monsters are converted to Pathfinder stats as needed. Deities and such are generally reused from the 3e/3.5e FR manuals and anything that may conflict we simply address on an as needed basis. But frankly, very little has needed to be resolved.
We are currently running the City of the Spider Queen module, which actually is a tiny bit easier in Pathfinder given the differences in rules for Haste and a couple other spells that the module relies heavily upon. Of course, our DM is making up for it in other ways.
Overall, though, it's been a fairly seamless transition for us to Pathfinder rules based in a Forgotten Realms world.
They're there for you, the DM, to create something.
The usual complaint about the Forgotten Realms is that too much is already written, making it hard or impossible to learn the setting for DMs, let alone the poor players, or for DMs to fit in anything of their own.
Having "blank lands" like this scattered around the setting leaves room for DMs' own creativity. If you have an idea, but can't fit it into one of the more popular playing regions because the lore and canon conflict with what you want to create, these blank lands are there to give your idea a home.
As a point of history, Sembia (south of the Dalelands) was a large blank area right in the middle of one of the most heavily-developed regions in the Realms, in the original AD&D 1e Forgotten Realms Campaign Set. It was set aside for DMs so that they could place their own kingdom (or expand a home game into a Forgotten Realms game by locating their existing campaign kingdom there) without having to settle for a region far away from the majority of Forgotten Realms setting material.
TSR promised to never develop Sembia so that DMs' creations would not be interefered with. That lasted all of six years before Sembia was written up in the AD&D 2e Forgotten Realms Campaign Setting, and a bitter hue and cry was the result.
So thank WotC for leaving you these blank areas. They gave you a name and an evocative description to set fire to your imagination — now follow your dreams and create something awesome that your players will love.
Best Answer
Yes there was, the cataclysmic event is called the Spellplague. Mystra dies, huge upheavals happen for a decade including natural disasters, arcane magic goes away for a time, etc. I don't think it escaped any Realmsian's notice, that's for sure; the effects were blatant and profound. The 4e guide is set in 1479 DR while the 3e one was in 1372 DR, so nearly a hundred years passed in world before the coming of 4e.