It’s a bit of a shot in the dark, but would you like to move up your memory limit? My guess is that your uploader fails on uploading big files with more serious plugins on just because they are using some of the memory too. In some cases “Memory exhausted” message does not appear if you don’t have the right server settings.
In any case you should have a verbose error message somewhere in the web server logs, as 500 means exactly this: “There is an error on the server side and I’m not showing it to you, visitor!”.