I've been using Synergy for a while on an iMac G5 running Tiger. I recently replaced it with a new machine (Mac Mini running Snow Leopard) and installed Synergy on it.
On the old machine, I used option-command-space as the hot key for play/pause, option-command-up arrow for volume up, etc.
On the new machine, the old hot keys all work except for option-command-space -- the Synergy prefs won't let me enter it. (I know that this key combination defaults to showing the Spotlight window, but I have unchecked that in the Keyboard preference pane.)
I wondered if this had something to do with Snow Leopard, so I installed it on another Snow Leopard machine, and it worked fine.
Well, that would have been my first idea as well (ie. that the system was intercepting that combination and sending it off to Spotlight before letting any other app "see" it).
Sounds like you've already tried everything that I would have tried. One other thing which I would give a shot is plugging in a different type of keyboard just to see if the results are any different. But really, no idea.
Thanks for the response. I've done a little more experimentation and come up with more information and a workaround. It looks like for whatever reason, you can't enter option-command-space in Snow Leopard. Maybe, as you say, the system intercepts the Spotlight shortcuts even if you turn them off. But you can enter it in Tiger as I had done on my old iMac. (I was mistaken when I said that it had worked on another Snow Leopard machine -- that machine was Tiger.) So I did the following:
Installed Synergy 3.4.1 (trial) on a Tiger machine.
Changed the hot keys as desired on that machine.
Copied the org.Wincent.Synergy.plist file from the Tiger machine onto the target (Snow Leopard) machine.
Installed Synergy 3.4.1 on the target machine.
Moved the plist file into the ~\Library\Preferences folder on the target machine, replacing the newly created plist file.
Open the preference pane and confirm that the hot keys are set as desired.
Download and install Synergy 4.5.2. Enter registration info.