I have a separate Main library with books I've cleaned up and converted to epub, and Special library withPDF's, cbr's, etc, which aren't necessarily even books. (I also have a separate "working" library for books I haven't yet cleaned up)
I find it convenient for exactly the reasons you describe. It keeps my Main library clean and relatively small so it's easy to transfer to my e-reader, tablet, or even putting it on an SD card with Calibre Portable. (Although now I keep them all on an external hard drive, so I don't do the SD card much)
It also lets me reserve Virtual Libraries for other purposes in each library, although if you're not using Virtual Libraries for something else, you could separate your libraries that way.
And of course, I use different custom columns in my Main library and my Special library, not to mention different View Manager settings.
I would recommend keeping your Mobi and Epub books together in one library, though, unless you have a real reason to separate them. Use the tag browser or Virtual Libraries to browse the different formats.
In the end, though, whether to separate books into different libraries or keep them together is up to you. There's no right or wrong answer, although a good rule of thumb is to keep them together unless you need different settings for the different libraries, especially custom columns.
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