I am going to have to go with the North/Silver Marches. The material on the area is really well written and gives great leads for adventures. The Silver Marches 3.0 book is great, but I have to say that the old "The North" boxed set is classic.
The city of Silverymoon is intriguing, and the politics of the land are pretty much in nascent stages, which always makes for interest in a game. The lands are ripe with adventure, and there are hooks everywhere. I really enjoy playing there, and reading about it as well.
That being said, if it is a one-shot, I might start in Waterdeep. It truly has something for everyone, as mentioned earlier by several others.
To answer your question about specifically staying away from documented areas, I have borne witness to such an act. On a PBEM that I play in, we started in Dragon Falls, in the Vast, and I am pretty certain that the eDM did that on purpose while he (and the rest of us) caught up on all the new material. Several of us, including him, had been out of the game since just after 2E came around. If you want avoid "metagaming" in your group, it might be the ticket to go to some far away land in the realms.
Good luck.