It's interesting that you ask this now. Just yesterday I was developing an IRC bot and a question like this came up; basically, how to write the negation of a regex.

The way I solved it was to add a new flag (not to Perl, but to the regex the users write), /r, that negates the return value of the match. So a user can do !grep /^ascended$/r to match all entries that don't match exactly "ascension". I haven't run into any major problems yet. :) I only match in boolean context (and without using any capturing variables).. I don't know if it'd work so well if I needed to do anything more complicated.