Looking for tips on debugging a network

Hi guys,

So, I've been doing WP for a while, but am still new to multi-site installs. I've suddenly got a huge bug, where new sites are being created, but they aren't maintaining their settings, and no content can be added - it just disappears.

Of course I have a bunch of plugins that I am running, many of which are network-wide. I'm imagining that the bug is because of one of them, but of course to test that, I have to go through and disable, etc.

But this is a live site.

So I guess I'm looking for advice about how to go about this. Any tips on debugging a live, running network? without losing too much time and interrupting the live sites?

And/or, anyone else see this kind of weird activity, where things just disappear on a new site creation? (older sites seem in tact and can still be modified..)