First off skip Maztica!
If you have access, the 3e FR campaign setting has a great trade route diagram on pg 88.
I once tried to run Waterdeep --> Nelanther (hunting kidnapped trade merchant) --> Chult (antidote for said merchant) --> Lake of Steam (Mercenaries to hunt those responsible for kidnapping) --> The Great Rift (kidnapper hidden refuge) --> Thay (kidnapper financier) --> Pirate Isles (group was captured in Thay and made slaves) --> Sembia (here they escaped) --> Cormyr (warn that trade merchant was impersonated and false goods poisoned) --> Savage Lands (where they died trying to hunt down enough dragons to fully arm themselves in dragon armor, shields and barding)
They had never played the Realms and I used it to introduce them to my favorite setting. Every campaign was held in a different area of the Realms from that point onward.
... AND ON THE EIGHTH DAY, GOD SAID, "I NEED A DRINK."