I used to live in Key Colony Beach, which is basically Marathon. I ran a 22' Bay Boat with a 225 Merc. while I was there. As long as the weather was nice, it was no problem to venture 20-25 miles offshore. Make sure you have a radio and cell phones with SeaTow, the Coast Guard, FWC and any other numbers you can call if you need to.
You are going a bit early for the good dolphin bite, but you could easily hook a sailfish right off the reef at the first drop. If you are looking for some eats, try snapper on the reef.
On a nice day, head out and try some trolling. You never know what you might find. As with anywhere, don't try to hard focusing on a species that you are having difficulity catching. Go with what is biting. I don't know if Dave is still doing his Thursday night semiinars at World CLass Angler - if he is, there is good information to be had for free.http://www.worldclassangler.com
Here's a good general keys fishing calendar.http://fishfloridakeys.com/chart.html