Strictly speaking, you don't really need to do anything to adapt humans to 0g per se -the body adapts to it just fine. You might even live longer.
The problem is mostly adapting to 0g without un-adapting to 1g. Once your muscles lean themselves down having gotten used to moving in 0g, landing on Earth may as well be landing on Jupiter.
The smallest change would probably be amplifying the body's response to physical stress: to wit, exercise less, gain more. Then it would take less exercising to maintain strength and allow for training up for an Earthside trip (or, perhaps, for a long burn). Alternatively, slow down the rate of muscle atrophy for similar results.
Beyond that, changes to the speed at which humans adapt to gravity changes would be valuable, to help cope with adaptation times and acceleration.
You'd want to avoid too many changes, though. Humans are pretty well optimised for Earth and if you go monkeying about too much with us it'd be easy to make us unable to survive on Earth anyway.