First let me clarify that I use Q2A and love it. But I may investigate a little more before having a really large site on this platform.
I have not tested the software for a large user base, but have tested it for large number of categories and questions (10M appx.)
Only a few things to keep in mind:
You may want to change the core files for somethings. Or atleast override some functions; if needed for yourr "large" site. I had to disable sorting functions for speed. but keep a log of these things so you can apply your changes after an upgrade too.
May want to use custom links through admin for some pages that may not suite your needs or to run some third party services.
Q2A supports four levels of categories. So, if you want more levels, you may want to tweak somethings. (I have already).
There is some caching plugin available. think about using that. I have not used it myself as it perhaps supports non-logged in users only.
In general pretty cool software.