First you need to decide which area of the Keys you want to visit. The upper Keys is the Key Largo area and I guess you can include Islamorada too. Islamorada is totally different than Key Largo though. The middle Keys includes Marathon, Key Colony Beach, etc. The lower Keys is from Big Pine to Key West.
If it were my first time to the Keys I would probably stay in Islamorada. Great fishing, restaurants, shops, hotels and it is close enough to day trip to Key West. I like the Caribbean Resort (
http://www.thecaribbeanresort.com/) and Breezy Palms (
http://www.breezypalms.com/) in Islamorada.
Check out this site:
http://fla-keys.com/
It may help you decide which area to stay.