Our web site has been under a constant development for a better part of the last five years. As it happens, pretty much all the styles for the site are in one big CSS file.
I had to do this about 3 years ago on a rather large classic ASP web application.
I took the approach that there are only a finite number of styled items on each page and started by identifying these. For example, I went through the main pages and identified that the majority of labels were bold and dark blue and that all buttons are the same width (for example).
Once I'd done that, I spoke to the team and we decided that anything that didn't conform to these rules I'd identified should conform, so I wrote a stylesheet based on this assumption.
We ended up with about 30 styles to apply to several hundred pages. Several regular-expression-find-and-replaces later (we were fortunate that the original development had used reasonably well structured HTML) we had something usable that just needed the odd tweaking.
The key points are:
You might also find that keeping unique styles (e.g. a dashboard page that has unique elements that don't appear elsewhere) in separate files to keep the size of the file down. Obviously, it depends on your site as to whether this would help.