Tony, I find this to be one of the hardest jobs when building an engine. When drilling a deep hole I start out with a center drill and drill it just a bit deeper than than the diameter of the drill you're going to use. This will give you an accurate chamfer for the drill to start in. Next, with a new drill, I drill the hole undersize. A resharpened drill, no matter how well it's sharpened, will sometimes wander as it drills. Now a take an end mill that has been reground just a little under nominal and counterbore the hole before starting my next drill. The last thing I do is run a reamer through the hole. You have to realize that if all the prep work isn't done well that the reamer will just follow whatever hole you have in there. I don't mean this to be condescending, and maybe you did all these preliminary steps, but I have had the same problems and this is the only way I could find to cure it. Now on to your dilemma. First off, what size are we talking about? If it's a standard inch or metric diameter this is what I would try to do. Get a long or extra long 4 flute end mill. Grind all of the flutes under size by .005-.008 except for the first .25 (cutting end). Now set up your piece, indicate it as square as you can get it and cut it with your modified end mill. Run the spindle at about 4-500 rpm. There should be enough rigidity in the end mill to cut the hole true. If you can't get a long enough end mill then you might want to consider making a cutter out of drill rod. After forming the cutting flutes on the rod just harden that area. This way the bar won't warp. What you're after is a rigid boring bar. If you can't get all the way through with the end mill, go as deep as you can then pick up and layout the the good center on the unmachined end. Set the job back up using the same surfaces as you did for the first cut, wiggle you layout lines and recut. This should get you darn close. What you suggested is viable, drilling and reaming first and then working from that hole to do the rest of the work but it's a pain in the butt.
George