Miami or Fort Lauderdale. Islamorada is--on trafficless day--an hour and a half drive from Miami. From Fort Lauderdale it's about a half hour further.
The Overseas Railroad hasn't been running since 1935, so Islamorada is only accessible by car (or boat).
Lots of time will be spent in water and sand, so be sure to bring a bathing suit, sandals, sunglasses, sunscreen, and party shoes that work for walking on the beach. Yes, it's Florida but it'll be December and it can get pretty chilly (yay!) and since we'll be on the water, it can get pretty windy too. So definitely bring comfy layers for all your get ups. Last but not least, we'll have some heavy hang outs so bring what you feel cute and comfy in ;D