Here's my advice:
1. Read, read, read! Read the next adventure all the way through before beginning play, and continue perusing it as your PCs make their way through the adventure. There are a LOT of details, and your players won't (and shouldn't) follow the trail of breadcrumbs exactly as the writers imagined - you'll need to be ready to handle off-the-wall questions and unexpected actions gracefully and without breaking continuity.
2. Similarly, read ahead as much as possible - it will help you foreshadow future events, introduce relevant NPCs early, etc. The writers wrote the AP sequentially and couldn't have perfect knowledge of what future chapters would contain. You CAN have perfect knowledge, though, so take advantage of that!
3. Build direct ties with important NPCs into your characters backstory. One of my PCs is the brother of Asrabey Varal. Another was Nevard Sechim's apprentice. Another is the child of two migrant workers on the Avery Coast Railroad. Another is the nephew of Catharine Romana and third-in-line for the Duchy of Shale. Little details like that will help your players get hooked into the setting, and will make it WAY easier for you to develop personalized side plots for each character.
4. Don't be afraid to simplify the setting. I think the authors wanted to make every possible option available to players, which is admirable, but many of them don't add much to the world. For example, I couldn't see how having both Dragonborn and Lizardfolk in Ber added to the plot, so I turned all the Lizardfolk into Dragonborn, which gave me more opportunities to develop Dragonborn culture and politics, personalizing all of it for the Dragonborn PC. Similarly, I turned all the gnomes into halfings because, although we have a halfling PC, we don't have a gnome PC. (In fact, our halfing player once commented, "We've met more Eladrin women than halflings," which is one of the things that urged me to develop halfling NPCs more fully.) If I were doing it over again, I'd get rid of Elves, too, since they don't add anything that Eladrin don't.
5. The large handouts (e.g. the dossiers) are amazing, but I found it more fun to re-write them to incorporate references to the PC's actions. Sure, you'll miss out on the cool formatting, but it's not too hard to print something with a typewriter font and then stain it with tea in the oven.
For example, here's the Royal Audit that Margaret Saxby did on my party.
6. If you're playing 4E, build the character mechanics on the backstory rather than the other way around. For example, if someone wants to play "a faithful warrior dedicated to Triegenes," I'd have them play a paladin. If, however, they wanted to play "a faithful Risuri warrior dedicated to the Unseen Court," I'd have them play a warden, instead. In fact, I limited class choices as follows:
- Risur: Primal & Martial classes (and fey warlocks)
- Danor: Martial classes
- Crisillyir: Divine & Martial classes
- Ber: Arcane & Martial classes
- Drakr: Arcane & Martial classes (and infernal warlocks)
And if it's useful to you, here's
the character creation handout I gave to my players back when we started, which includes a brief summary of the nationalities, races, and classes available to the players and describes what makes them easier or more difficult.
Good luck!