I have made a few apps for people which primarily takes their large protocols (single pdf file) and breaks it down into several subsections making it easier to use and find the information you need. I use a program I got on the mac app store called PDFSuite to help extract the relevant subsections and save them as their own pdf. However, I have found that if I start with a single pdf file around 6 mb and break it down into say 50 individual pdfs, the final size of all the individual files together approaches 20 mb. Is there a way around this? Shouldn't they all add up to 6 mb?

PDF's are bloated full of cr*p, you're basically creating multiple pdf's, each one full of all the bloated code for an individual pdf, hence equalling much bigger than the original. There are various tools online to reduce the size, just do a google search. Depending on your application I find the best tools are ones that convert everything in the pdf (including text) to small jpg images. The results are just like a regular pdf but much smaller. There are various free compression tools online too, efficiency varies depending on the content of the pdfs.

This is one tool I use, it's free but it adds a watermark to the footers: http://www.cvisiontech.com/online-conversion/general/main.html?lang=eng

We may be doing the same thing... Anyway, when I extract the pages and crop them the resulting pages are on the order of 40k or so. I'm using Acrobat Pro 9. I have PDF suite. It's, well... I use Acrobat Pro 9.

If you use File > Save As > Optimised PDF in Adobe Acrobat Pro X, that can shave loads off your final file size, really depends on functionality within your PDF, version, document size, etc.. but it will help massively.