I don't think there is a definitive answer to this question at all. For one thing, I think what suits one person will not suit another. Moreover, people differ in how many entries they have to handle, where they obtain new data from and what they need to be able to do with that data later on.
However, I realised that trying to explain this in comments was not working very well. Maybe this will be a little clearer.
Overview
I currently use different files for different kinds of abbreviations. One for author, editor and organisation names. One for journals and series. One for places. One for publishers. One for everything else. Then I have bib files by category e.g. one for general reference (dictionaries etc., regular non-specialist non-fiction), one for literature etc. This makes it easy to cross-reference because all entries for papers in a given anthology, for example, are in the same file as the entry for the anthology. (Note that not all of the required data is in the same file. But neither bibtex nor biber care about that.) Then I have some scripts for transforming downloaded references into my preferred format.
Example
Hopefully this will make the above a little clearer...
Suppose I have an anthology of papers on aardvarks edited by Camel B. Jones which contains a paper on their diet by Maria N. Davies.
Camel B. Jones (ed.). 1992. The Life and Times of Aardvarks. Oxford: Oxford University Press.
Maria N. Davies. 1992. 'What Aardvarks Like To Eat'. In Camel B. Jones (ed.), The Life and Times of Aardvarks. Oxford: Oxford University Press. Pages 141-156.
Then in authors.bib, I might have:
@string{davies-maria-n = {Davies, Maria N.}}
@string{jones-camel-b = {Jones, Camel B.}}
In pub.bib, I might have:
@string{oup = {Oxford University Press}}
places.bib might contain:
@string{oxon = {Oxford}}
Then zoo.bib might contain all entries to do with zoology. For new keys, I try to use something like lastname1-lastname2-...-initiallettersoftitle so my entries would look something like this:
@incollection{davies-wal2e,
author = davies-maria-n,
crossref = {jones-lta},
title = {What Aardvarks Like To Eat},
pages = {141--156}}
@collection{jones-lta,
editor = jones-camel-b,
publisher = oup,
address = oxon,
title = {The Life and Times of Aardvarks},
booktitle = {The Life and Times of Aardvarks},
year = 1992}
The idea is to ensure consistency by using strings for things which are used multiple times (or might be used multiple times). Titles are unique - or, rather, they do not vary in consistent, patterned ways. So they go in in the normal way as there is no point in bothering to define strings for them. But anything where consistency is an issue gets a string defined in the appropriate file of abbreviations.
Now, if I need to cite 'What Aardvarks Like To Eat', I of course need to load all of the relevant bib files in the appropriate order. That is, I need to load the files containing the strings before loading the .bib files which use them. For example:
\bibliography{authors,pub,places,zoo}
But that's just code you copy and paste into a new document, put in a template or load using \input.
@usernotation, the addressee will get a notification about your comment. (The originator of the question will always be informced.) You write 27 files, which suggests you have one file for surnames starting with a, one for surnames starting with b, and so on, and one for digits. This really doesn't make sense to me and in my comment I tried to explain why I thought it didn't make sense. I don't have my own system of authors; I just have one large bibliography file. – Mar 04 '14 at 13:49.bibfile, which you use while composing all documents or books (etc.). Once, say, the article has been accepted by a journal and the reference list will be more or less frozen, use a tool -- eitherbibtoolif using BibTeX orbiberitself -- to extract the citations you are using for that article into a separate.bibfile unique to that article. This solves virtually all danger of reduplicating entries, having identical keys, etc. For entry keys, use lastname+year, and lastname+year+1st letter of 1st 4 title words to disambiguate. – jon Mar 04 '14 at 15:43