God, I'd love to say "Get Dark Sun!" but honestly, it doesn't sound like a good match. "Grim and Gritty" doesn't really work until at least the age of sixteen, in my experience.
I think DannyAlcatraz is dead right in his assessment: look at what your audience is into, and go from there. My guess is that Eberron is your best bet - there's already 4e materials, there are prepublished adventures in DUNGEON (my advice is to use them as a framework, and then modify to your heart's content - it's the ONLY way to run wotc in my mind), and there's a lot of different areas you can include for multiple campaigns.
I'd recommend were you to do that, that you have all the PCs belong to the same organization - members of the Twelve (an alliance of dragonmarked houses), the University whose name I forget (Indiana Jones adventure for the win!) or maybe even a MOSSAD-type agency whose goal is to bring to justice war criminals or something. That way, you can easily mix and match PCs from different groups, and have an excuse to send the PCs all over the continent - and Eberron really excels when you play John Williams' music and trace a red line over a map.
As for Forgotten Realms - I was never a Realmsie, and the 4e version was so-so for me. There are definite plusses, and definite negatives. My gut would suggest it's a pretty decent starting point, and there's plenty of room for a GM to create his own worlds. One day I'll run a campaign set in Damara and have a ball.
