Ok so I snagged some flights to Miami in November for myself, my wife my (by then) 4 and a half year old and my (by then) as yet in arrived 9 month old. We have 2.5 weeks(ish) in Florida and I'm trying to work out an itenarary. We get there on a Thursday, leave on a Sunday so I'm figuring something along the lines of a couple of days in Miami to shake off the flight, then drive up to Orlando for a week or so of Disney and the like. The question is what to do for the final week. I was thinking about the keys but don't know how kid friendly they would be, so any suggestions welcome.

You could come back via Tampa Bay. Do Busch Gardens, they have a great kids area and it has some good animal viewings. A day at Clearwater beach. Maybe do Weeki Wachee for a day. Head down 75 and drive across Alligator Alley stopping in the everglades. Billy's Swamp Safari is a tourist trap but I bet the 4 year old would love it.

I would think that four and a half year olds like animals. Look for alligator farms, seaworld type places, the state park with manatees (Homosassa?), the Monkey Jungle outside Miami, multiple good zoos scattered across the region (not where you'll be but locally we have Zoo World in PCB) especially perhaps the ones where you can feed the animals (at Zoo World you can feed giraffes and budgies) or pet them.

Zoo Miami is a great zoo for animals.
There is also a brand new Children's museum there for the 4 yo.

Where are you flying back out of, Miami? There are some cool kids oriented things to do in the keys. Somewhere I posted a bit of a guide. But off the top of my head in the keys - Key Largo has Pennekamp state park that has a glass bottom boat tour of the reef. There is a very interactive bird rescue park.
You can feed the tarpon fish up close at Robbie's. Theater of the Sea is a smaller version of the shows at Sea World.
If you venture all the way to Key West, you can take one of the trolley tours, visit the treasure museum and of course, the entertainers at Sunset at Mallory Square (though some language is PG-13).

The Kennedy Space Center is a short ride from Orlando and may (or may not) be worth it.

What do the adults like to do?

Oh yes....zoos! Tampa has Lowery Park Zoo. It is awesome. You can ride a camel there! http://www.lowryparkzoo.org/

Thanks all for the suggestions, zoos were definatley on the radar. On the keys, any suggestions on which to stay on (if we do end up there)? I've heard one of them (key largo I think) is just full of bars for college kids and the like so would rather avoid. The other place I've heard is nice is Clearwater beach near Tampa so that is another option.

As for the adults, me I'm a massive geek so Kennedy is definatley on the list and my daughter likes that kind of stuff as well. My wife has never been to Florida before (I have many times as a child and an adult) so she is yet to experience the whole Disney thing.

Key West is the one full of bars. As long as it isn't Spring time, not a ton of college kids. All of the bars (well, most) are located along Duval street. You do want to avoid it with kids in tow at night.

Key Largo is not too far of a drive. It is central to Pennekamp, a fairly short drive to Theater of the Sea and Robbie's.

Clearwater is a bit of a hike from Orlando. But nice beaches. There is a new Children's Museum in Tampa, which is on the way from Orlando.

We just did a similar trip last year with a 3 year old and less than one year old and had a blast.

The kids loved Alligator World (which has much than just alligators), Sawgrass Lake Park in St. Petersburg (public park w/ wild alligators, turtles, and frogs you can see on a nice trail), Anne's Beach in the keys (very calm water, kids loved the hermit crabs), Cape Canaveral (we were able to watch a rocket launch while we were there), a helicopter flight in Orlando (only $63 for all 4 of us), Fort DeSoto State Park (watching dolphins from the pier and great sand for playing in), South Florida Museum (has a great planetarium show and Snooty the manatee) and just hanging out at the Sheraton Vistana Villages pool and enjoying the resort activities.

Things we tried to do that we wouldn't do again were Clearwater Beach, which just didn't have much for our age of kids (probably better for older kids), airboat tour (too loud for the kids). I wish we'd had time to do the Tampa Zoo and the Miami Seaquarium.

Pretty obvious, except for the Baby Care Centers, but helpful none the less.
Important things to know when visiting Walt Disney World with an infant or toddler

South Florida is barren of activities for small children when compared to Orlando or even Tampa. I suppose we have a few amusement centers here and there (Rapids Water Park -- but largely useless for the ages listed in the OP, maybe Miami Seaquarium?), but they are mediocre at best. The true child centered hub of this state is Orlando, as I've said many times on this forum before, South Florida has very little in the way of early childhood attractions. Bite the bullet and stay in Disney World for a few days.

As for "other than the obvious" the few hole in the wall quality venues are generally bars or restaurants i.e. not child friendly.

-LPDAL

Thanks again, at least half the time we will be in Orlando I guess the question is whether we should extend that. I'm not booking anything yet (will be airbnb'ing an apartment) so have plenty of time to mull it over. What's in Tampa?

Not a whole heck of a lot. But it is close enough to Orlando that you could do a day trip easily, especially if you are staying near Disney.

Lowry Zoo. - A good zoo, better than any in Florida, except for Miami.

Glazer Children's Museum - Brand new and right near....
Florida Aquarium complete with interactive water zone

Museum of Science and Industry - definitely geared toward young kids

Big Cat Rescue - could be combined with the Science and Industry visit

A bit further afield
Dade City Wild Animal Park - A wildlife sanctuary

Ringling Museum - Both a circus and art museum. The art museum is housed in his mansion.

You used to be able to rent fishing gear and feed pelicans at The Pier in St. Pete. IIRC, that's been demolished. Is there another place where you can drop a fish in a pelican's mouth? My kids found that quite entertaining.

I believe you can no longer do that. It is illegal to feed wild birds now.

This. It trains them to get food from fishermen. They end up grabbing the bait while the fisherman is casting it, hooking the pelican.

You can still feed tarpon at Robbie's in Islamarada.