What one single resource should I read before playing in my first ever 4e Forgotten Realms campaign?
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The D&D 4e forgotten realms handbook was very well laid out. It describes the more recent changes that make it fit into the 4e world.
The 4e Forgotten Realms Players Guide is all you need, even if you are completely new to the Realms. It's entire reason for being is so that there is just one book to go to that gives you an overview of the setting.
For 4e, as Scott notes, the Forgotten Realms Player's Guide is pretty good. Since there've only been two 4e Forgotten Realms books so far, it's kind of the default choice. WotC has announced the Neverwinter Campaign Guide as a 2011 release, but that won't come out until fall of 2011.
If you're wanting game mechanics as well as lore, then the FRPG may be more important. You can get them from the Character Builder as well, but you may be the kind of person who likes to have them on paper for easy browsing.
For 3e, I think the 2002 Forgotten Realms Campaign Setting is superb. It does have a lot of GM material in it, so check with your GM before you read it if you haven't already. Since there have been so many changes in the Realms in 4e, it won't be as useful to a 4e player, unfortunately: otherwise I'd recommend it over the 4e version. What it would do is give you a really solid grounding in the history of the Realms.
If your campaign focuses on a specific area, it's possible that one of the 1st, 2nd, or 3rd edition books about that area might be more useful to you. Again, this is something to ask your GM about.
As a supplement to most of the above, Candlekeep is the best Forgotten Realms fansite on the Internet. It won't help much at all with the 4e time period, but for anything else it's a great alternative or add-on to any book you could read, and it's very good for getting a picture of the history of the Realms.