If you disable a plugin (don’t delete it), the settings should be preserved for when you reactivate it.
s2member and other membership plugins are pretty complicated and may cause performance issues… especially if you are on shared hosting or a host that severely limits the # of simultaneous database queries. If you manage the server yourself, increasing the MAX_CONNECTIONS property for MySQL can often help with stuff like this. (e.g. if your host limits simultaneous queries to 100 and you typically have 80 queries, but 280 with s2member activated, your page loads will be 3x as long.)
The other performance issue to think about with membership sites is that having pages different based on membership level breaks any caching you may be doing. So maybe you have good load times because of caching, and when s2member is enabled, your site can’t be cached anymore.
Here are some plugins to help you troubleshoot performance issues with WordPress:
http://wordpress.org/extend/plugins/p3-profiler/
http://wordpress.org/extend/plugins/debug-queries/
http://wordpress.org/extend/plugins/blackbox-debug-bar/
FWIW, I’m the developer of Paid Memberships Pro, a competing membership plugin for WordPress. (It’s totally free in the WordPress repository: http://wordpress.org/extend/plugins/paid-memberships-pro/)