Can Perl even handle files "a few good GBs" in size?

I hear Perl's regexp are not quite as fast as the tools in order to accomodate its more powerful features. Have you tried benchmarking? The real difference, however, will be determined by how you write the regexp. There are often efficient and inefficient ways of writting regexps.

Unless you have "a few good GBs" of memory and then some, line by line should be faster.