Personally, I have two different bib-files; one for publications by others and one for my own publication list. But even this is just a matter of convenience because the entry-groups differ between the two for a more convenient working with the bib-files themselves, not considering any LaTeX compilation.
My main bib-file is well in access of 1000 entries, and I never experienced any problems with any compiler (BibTeX, BibTeX8, BibLaTeX) so far. I have never heard of any instance where such problems occurred either. True, there is a limit for the number of possible bibliography entries (defined by bytes to be processed) in BibTeX, and also in BibTeX8 (altough in the latter you can expand that limit to such large values that I did not run into problems with my Diploma thesis which contained tons of citations). But this has to do with the number of citations in your document and not the file size of the bib-file, so if you run into this problem it would persist even if you would split your bib-file. As far as I know, BibLaTeX does not have such limits anymore at all.
Another thing to consider is how easy it is to merge entries from multiple bib-files into one bibliography. In BibLaTeX, where you can declare several source files easily and create the bibliography by an altogether different command, this is easily done. In BibTeX and BibTeX8 it is to my knowledge not so easy (if possible at all) to compile information from several bib-files into one reference list.
So I would say is it mainly a matter of personal taste, probably also depneding on how much you are using the bib-files directly---it can make sense to have several if the entries are very different in topic. Compilation will work with either version at least in BibLaTeX, but may require additional packages or merging of bib-files for BibTeX/BibTeX8.