Habe mit so großen Dateien leider keine Erfahrung.
Aber ich würde in besonderen Fällen mal bei LWP::UserAgent (die "unsimple" Version) stöbern.
Beim ersten Reinschauen traf ich auf diese Aussage:

If you set the $DYNAMIC_FILE_UPLOAD variable (exportable) to some TRUE value, then you get back a request object with a subroutine closure as the content attribute. This subroutine will read the content of any files on demand and return it in suitable chunks. This allow you to upload arbitrary big files without using lots of memory. You can even upload infinite files like /dev/audio if you wish; however, if the file is not a plain file, there will be no Content-Length header defined for the request. Not all servers (or server applications) like this. Also, if the file(s) change in size between the time the Content-Length is calculated and the time that the last chunk is delivered, the subroutine will Croak.

Quelle: http://search.cpan.org/~gaas/libwww-perl-5.69/lib/... ganz unten.