I use a Revelate Tangle on a 58cm road bike frame, and did not lose bottle access. You would however lose DT shifter access, and a bare rear brake cable might be problematic. I ride SS, with fully housed brake cables, so no issues there.
On the knee rub, it was totally unnoticeable on the tangle when seated, and the only time I remember my leg rubbing it was on some hill climbs with a lot of standing and heavy bike movement. And I ride with my knees close to the top tube.
It is an incredibly well thought out bag.