I have had this same issue, in my situation it has always been when someone else has the geodatabase open and is editing. If I have them close out, then it saves without a problem. I have looked at the lock files in the file geodatabase to determine what kinds of locks there are on the files. It is frustrating because I can't stop someone from opening an MXD and accessing the geodatabase, so if I am in the middle of editing I am stuck.