There are now tools available to organize scripts and stylesheets, what you need depends totally on what development environment you're running it in. What is clear is that you don't need to maintain one gigantic file.
Bundling and minification
In a deployed environment you want to keep the number of requests that users do on a web page as low as possible. The reason for this is that you get faster page loads if less requests are done.
However that doesn't mean that you need to develop it as one file; you can use a build tool to concatenate the source files as one. And once you have a build tool to concatenate you might as well want to minify it (so that it takes less bytes send, which is a good thing).
The easiest way to get started is to write some batch script or a build script that concatenates the files and runs the concatenated file through a minifier such as the YUI Compressor. There might however already exist in your development environment tools that do this already.
Other than that I prefer to use superset languages such as Less or Sass/Compass to create my stylesheets. The extra features you get is awesome, such as: variables, arithmetic, mixins, helper functions. Once you use it you rarely want to go back to write vanilla css. Here the process is the same as above, you compile (or have the tool watch for changes) the source down to the file that eventually will be used.
In MVC4.NET I prefer to use the built-in System.Web.Optimizations bundling feature with BundleTransformer so I can use superset languages (it also works in MVC3 but requires some configuration to do). It is pretty much automatic, you can see the actual sources while developing and once the debug flag is unset it will compile and minify the files automatically for production environment.
I also use superset languages in other environments, mostly the ones that are easiest to use:
- nodejs have stylus pretty much natively for stylesheets, and coffeescript is quite easy to get it working
- ruby/rails has sass/compass natively and coffeescript has been supported by the community for a long while
Other tools worth mentioning