Sorry for the delay. I have not yet had the chance to test this on a clean install, and doubt i'll be able to do that anytime soon. I did, however, try on another test multi-site we have, with the following results...
Uploaded akismet.php only (with no key hardcoded) and activated it successfully on main blog. Attempt to activate on sub-site with no other plugins activated resulted in the same error as above...
The plugin generated 618 characters of unexpected output during activation. If you notice “headers already sent” messages, problems with syndication feeds or other issues, try deactivating or removing this plugin.
Deactivated plugin from subsite, hardcoded the key, then reactivated it and got the same error again.
Server logs during this time indicate the following:
[error] PHP Warning: include_once() [function.include]: Failed opening '/home/maindir/public_html/wp-content/plugins/legacy.php' for inclusion (include_path='.:/usr/lib/php:/usr/local/lib/php') in /home/maindir/public_html/wp-content/plugins/akismet.php on line 45, referer: http://url.hasbeen.changed/wp-admin/plugins.php?deactivate=true&plugin_status=all&paged=1
Deactivated plugin from substite and main blog, uploaded Akismet folder including legacy.php and then successfully activated plugin on main blog and subsite without any errors.
Both sites are running WP 3.0.1 MultiSite, with Aksimet 2.4.0. Hope this helps.