I was at a LAN the other week and to make sharing files easier we use a program called DC++. Shortly after trying to download the first few files I got a confusing error. "could not open target file: the system cannot find the path specified" After spending much time looking around the web and asking friends at the LAN we finally figured out what it meant.
In the Settings window and under the Downloads section you designate two directories, one is a default download directory and the other is an unfinished donloads directory. I had these two options set to directories that did not exist, a quick change however did not quite work as while the folders exist they were under an account the active account could not access, a final change pointed these options to two directories that existed and the account could acces. This fixed the problem right up.
So here's a little picture to show the two offending text boxes. Set these to folders your account can access, folders on your desktop for example, and that error should disappear.