What is a screen reader but something that can read the screen? It needs metadata from the GUI, which ought to be available if the system is correctly architected. It needs navigation order, which ought to be something that can be added later with a separate metadata channel (since navigation order should be completely decoupled from the implementation of the GUI).
The other topic of accessibility a la Steve Yegge: the entire system should be approachable to non-experts. That's already in their mission statement.
I think that the systems of the past have trained us to expect a lack of dynamism and configurability. There is some value to supporting existing screen-readers, like ORCA, since power users have scripts and whatnot. But my take is that if you provide a good mechanism that supports the primitive functionality and support generalized extensibility, then new and better systems can emerge organically. I don't use accessibility software, but I can't imagine it's perfect. It's probably ripe for its own reformation as well.