Do you over/under pronate? I was told that over/under pronation can be a big risk factor for sprained ankles. Surprisingly, overpronation is apparently worse for the outside ligament - which I've sprained many times... Orthotics seem to correct it for me (touch wood!).
Like you I used to get lots of headaches, and I'm overwieght. It seemed to be down to a combination of dehydration and lack of salt/electrolyte for me. Plenty of electrolyte drinks and gels early in a run sorted me out fine. I can always tell when I've not had sufficient salts - quick chug of SiS Go! and I'm much better.
(Tip: cheap electrolyte drink - half orange juice, half water, pinch of salt (sodium), pinch of LoSalt (potassium)).