April is a good time to come, but not ideal IMO. Still high season, so lots of expense and lots of people. I think November through February is better (of course, Christmas week and Thanksgiving week are going to be pricey and crowded). But March through mid-April is just way too crowded for me - I want to get out of here, ha.

All of the Keys are different in their own way, if you spend time here. Some of the things that shock people are: there are no "beaches", and most access to water is privately owned. There are some nice, public, man-made beaches like Sombrero Beach in Marathon, but another surprise to most is there are zero waves, since we are surrounded by shallow reefs.

I would recommend getting out on the water over the reef, if you can. Maybe a snorkel excursion to Looe Key. The beauty is truly breathtaking - for now, anyway...

Key West is definitely a place I would schedule the bulk of my time, though. It is a unique and memorable place - I get a room there once in a while for a mini-vacay, and love it.

If you are into fishing, I would probably choose Islamorada for a charter. You can choose back country (Florida Bay), the reef (oceanside), or offshore (usually out to the Islamorada humps).

When you get closer to your trip time, and know the areas you are staying, I'd be happy to give more specific advice. I'm fairly familiar with the whole 100 miles.

Here's a typical shot of what you might see at Looe: