Although the astronauts can comfortable work in any orientation, the shuttle is generally designed as if the roof were "up" and the wheels were "down".
Of course, the whole cockpit has to be designed like this since the astronauts are in it during landing when there definitely is a difference between "up" and "down".
But if you look closely at the pictures in the links below, you will see that in the work area, most visual cues (like signs and labels) and the workstations are also all oriented in this way.
This means that the astronauts GENERALLY work with the roof being at their heads, which thiers brains will interpret as being "up".
Interestingly, the space shuttle actually flies upside down relative to Earth (the roof and open shuttle bay is usually facing earth).
But even with the windows, the astronauts don't feel like they are upside down- to them, the Earth is just above their heads.
http://www.nasa.gov/images/content/124678main_s114e7127.jpg
http://www.nasa.gov/images/content/124681main_s114e7129.jpg
http://spaceflight.nasa.gov/gallery/images/shuttle/sts-114/lores/s114e7111.jpg
http://www.nasa.gov/images/content/124669main_s114e7012.jpg
http://www.nasa.gov/images/content/124666main_s114e7001.jpg
As I mentioned above, the shuttle generally orbits with the "top" (or "roof" or "bay doors") pointed towards earth.
However, if two shuttles were to meet in space, they would be oriented in whatever manner was appropriate for the maneuver they were attempting (docking, payload transfer, etc.)