As far as actual routing, I consider the ICW through Biscayne Bay to Channel 5 just South of Islamorada and then crossing over to Hawks Channel for the remainder to be the best route. It is direct and scenic and offers protected water and plenty of anchorages as well as plenty of interesting stop overs.
A note: When in the ICW in the Upper Keys the water to the North is Everglades National Park. This doesn't really effect travel but be advised if you wander to starboard you're in the Park and there are additional rules.
As mentioned No Name, Boca Chita and Elliot Key are all good first anchorages in the Bay. In the Upper Keys, again as mentioned, Pumpkin and Tarpon Basin make great anchorages. In Blackwater Sound you can anchor off the Caribbean Club (where the movie Key Largo was filmed) and dingy into Sundowners for dinner
Key Largo Restaurant offering waterside in the Florida Keys: Sundowners
Buttonwood Bay between marker 54 and 55 is a good anchorage (as long as the wind stays East) and is near "downtown" Key Largo. Snooks has good food and is an easy dingy ride
Key Largo Restaurant, Key Largo Weddings, Key Largo outside Dining, Wedding Reception, Snooks Bayside Restaurant and many stores are close by.
Near Snooks the Upper Keys Sailing Club welcomes transients and has the best sunsets in the Upper Keys. Dockmasters Guy and Sally monitor 72 or e-mail or call:
HOME | Upper Keys Sailing Club They can accommodate your draft at least on the end dock.
As mentioned Plantation Yacht Harbor, now Founders park is an excellent marina with many features.
Islamorada, Village of Islands Florida
Next, as previously mentioned in Barley Basin is the Lorelei as well as Bass Pro
Lorelei Cabana Bar And Restaurant - Islamorada Florida Keys - Join us at the Lorelei Cabana Bar and Marina for Breathtaking views of our world famous Sunsets and Live Music 7 nights a Week Lorelei is highly recommended for a sunset dinner.
A little further South (West) is Indian Key State park which includes Lignum Vitae Key. A great day trip to Indian Key that has a very checkered history
Welcome to Florida State Parks and very close by a favorite tourist stop is Robbies Marina where for a couple of bucks you get a bucket of pinfish and get to hand feed 100lb wild tarpon
Robbie's in Islamorada, Florida Keys: Fishing, boat rentals Very touristy but worth the stop, just don't lose any fingers.
South (West) of here you cross over to Hawks Channel for the trip to Marathon. Enter between Knights and Boot Key in the well marked channel from the west end near the 7 mile bridge for several marina options.
As previously mentioned Bahia Honda State Park is a good anchorage with one of the few white sandy beaches in the Keys. Interesting geography that there are few "traditional" white sand "Florida type" beaches in the Keys, people kind of expect them, there are a few but not many.
A very nice anchorage further west is Newfound Harbor. As you enter to starboard will be the very exclusive Little Palm Island Resort
Florida Keys Resorts | Florida Keys Hotels | Little Palm Island Resort where long ago PT109 was filmed. If you enjoy snorkeling Looe Key is a very nice dive straight offshore
Looe Key National Marine Sanctuary | Big Pine Key & Lower Florida Keys
From there its a short hop to Key Weird where I lived for quite some time, not sure how long. I am told I had a very good time and I'm sure you will too.