I recently installed Yet Another Related Posts Plugin (YARPP) and started experiencing problems with settings not getting saved, similar to what others have reported. I disabled W3 Total Cache (W3TC) and the problems went away. So I reenabled W3TC and selectively disabled parts of it until I isolated what was causing the issue.
I use Amazon CloudFront as a pull CDN. I had listed the plugins directory in the list of custom files to host with the CDN. As soon as I removed this, the problem went away.
My website has been live for about a year and I have about 50 plugins installed. Thinking back, I experienced a similar issue with Newsletter Sign-Up when I launched the website that I never quite resolved. I have not gone back to test this, but my hunch is that this other issue has just gone away, too.