A couple of months ago, GTA:SA refused to start after a driver update (no symptoms really, the game just would not start). I didn't have time to pursue the problem at the time -- I have completed all the missions and don't really play the game too much now, but it is still fun to pick up now and then.
Now after a couple of minutes googling, I found some posts indicating that a corrupt user-settings file called gta_sa.set may cause these exact symptoms. I deleted the file (it's in the My Documents\GTA San Andreas User Files directory), and now the game starts.
I'm off to running over old ladies again!!!