There are different areas that problems occur:

• hotkeys — do keyboard or mouse hotkeys work while the remote desktop is in focus?
• inject — can you 'send' keystrokes and/or mouse clicks to the remote desktop?
• UIsubsys — what sort of data you can get back from the UI subsystem (eg. window titles, locations of discrete windows, etc) — You quickly realize that you pretty much NEVER get this, unfortunately. At best, you can read individual pixel values.

VirtualBox

• [hotkeys] they won't work when GuestAdditions are installed

RealVNC

• [hotkeys] most work, but some combinations involving the Windows key (eg. "#a") don't work without modification (ie. to "LWin & A")
• [inject] AltTab and AltShiftTab don't work when VNC has focus (workaround: use VistaSwitcher instead, it works even when VNC is up

Synergy