I had a Revelate "Gas Can" bag, which is reasonably large" combined with a saddle bag and on my new bike decided to ditch them both for a smaller frame bag (Banjo Bros. "Minnehaha" medium). I am much happier with this setup so far, honestly:
My frame is a 61 so it may hog up a bit more space on a smaller frame. The Revelate is a well-made bag but the floppiness of it annoyed me, even though it never interfered with my pedal stroke.