I've responded on your blog, but I'll post it here as well for other people's reference on the issue:
[Mon Mar 19 16:17:21 2012] [warn] [client 0.0.0.0] mod_fcgid: stderr: PHP Fatal error: Call to undefined function is_main_query() in /home/www/domain.com/wp-content/plugins/simply-exclude/simplyexclude.php on line 1913, referer: http://domain.com/wp-admin/plugins.php?activate=true&plugin_status=all&paged=1&s=
(note: mod_fcgid logs all PHP errors as "warn" level, regardless of their actual severity -- and in this case, it's actually a Fatal PHP error [as noted beside "stderr:"])
Fatal PHP errors result in display of an Error 500 under Apache -- so I'm 100% correct in what I reported ;)
The is_main_query() function is new as of WordPress v3.3 (http://codex.wordpress.org/Function_Reference/is_main_query), so it breaks compatibility for anyone on a lower version. Currently, your plugin is listed as requiring v3.2 or higher (I'm on v3.2.1).
I'm fine with reverting to v2.0.2 or holding off on re-activating it until I make the move to WP v3.3+ -- not ready/able to just yet. It'd be great though if you could manage to rework it to have compatibility with <v3.3 for all of us who are, for whatever reason, a couple versions behind.