I've thought about the same thing. I have a Tacoma so I have a full size spare, but it's mounted under the bed like most trucks. So I'd you're out on the trail in some messy stuff, you don't want to have to get down on your knees and start cranking the spare down and have to drag it out of the muck to mount it. Plus if your bed is full of your gear, then you gotta put the flat back up under the bed too. So many people like to reroute to a rear swingout or similar.
As for ideas for reusing the spare tire space, I thought a lot about it and the usage would be best suited for something that you don't need access to easily or often, and something that is potentially applicable whether you're offroading, camping with family, or daily driving. For that reason, the best use is probably additional fuel storage. I know there are a couple places that will add a secondary fuel tank to a Tacoma.
However, I thought about what I always bring overlanding but would be great to be able to hide it...water storage. I also like that, just like a fuel tank, the water would be down at a level that distributes the extra weight evenly between the rear wheels, rather than a large jug sloshing around in the bed.
Those are my ideas so far at least. Looking forward to seeing other people's.
