I did some research on this when I saw PD4 had finally been released, because I'm considering getting a CLIE.
If you're using a Mac with IRDA support (e.g. a TiBook) you can sync any CLIE over the IR port without any additional software.
If you don't have IR support, then any CLIE with PalmOS 4.0 or later will sync with no additional software needed. You only need The Missing Sync if you're using a CLIE with PalmOS earlier than 4.0.
The only thing TMS provides you that Palm Desktop won't is the ability to mount the CLIE's Memory Stick on the desktop, which can be achieved just as well using a USB or PC Card Memory Stick drive. I'm using Sony's PC Card reader right now in conjunction with my Sony digital camera, and it works like a charm in OS X. In fact, one cool feature is that if I put in a Memory Stick that I've used to take pictures, iPhoto launches and recognizes the Memory Stick just like if I'd plugged the camera into the USB port. Which means I don't have to worry about carrying the transfer cable around, or using my camera's (annoyingly short) battery life to transfer pictures.