There's only a minor chance your LW main settings would be changed. Perhaps things like program interface size, columns to show etc might be lost. At worst, your shares information might be lost.

In case you wished to know, the important files to backup from the LW preferences folder are: (note: you may not see the .dat extension if your system is set not to show file extensions:)
library5.dat = lists all your "shared" files. (I occasionally back this up, because I have 3 sets of shares for different purposes. eg: mostly music, or mostly videos, etc. Also in case something happens, I can always use the backup.)
library.dat = lists sensitive folders & files not to share. This file is not so important. (LW 4 used this file-name for the equivalent of library5.dat's purpose.)
downloads.dat = keeps record of the file download history & % downloaded of each file downloading. This is a very important file.

These files should never be returned to the LW preferences folder to replace others when LW is open, else they will simply be written over with whatever settings LW is presently using.

spam.dat = keeps record of types of files marked as spam.
tables.props = lists custom set tables & their widths.
limewire.props = General settings. Includes interface size, filtered extensions & keyword filter, banned ip addresses, up/download settings, etc.
gnutella.net = connection file.
fileurns.cache, not sure the purpose, but related to files "shared". This one could be worth backing up if backing up library5.dat
ttdata.cache, not sure the purpose of this file.

I occasionally get this error also in the Upload window. In LW 4 I think it usually meant the file was no longer being shared. For LW 5, I'm not sure what it means. I'd be purely guessing the cause.