Okay, this one isn't exactly node based, but the connections have a real world feel and intuitiveness that makes working with musical instruments as intuitive as hooking up a guitar pedal.

Reason is my synth of choice these days.
http://www.propellerheads.se/

If you want to design your own synth...Reaktor.
This thing has a super steep learning curve if you're unfamiliar with signal processing.
Awesomeness, you can really get your hands dirty with the synth AND interface design...but that's also the drawback...you will burn days and weeks if you start something from scratch.

http://www.native-instruments.com
Reaktor ftw.

I'm sorry, but you'll need to download the udk and get into the material editor to get to this one.
Node based shader editors have really taken off in the last two years. This one is quite quirky in that it reads right to left. It has some other annoying aspects but you have to trade your complexity for assumptions, and your flexibility weighs against your optimization.

http://www.udk.com/

VVVV, definitely the most versatile node based editor I've seen. Really love the array interface. Not so happy with the quirkyness of the UI. It has a very even learning curve because you can dive into existing patches for instructions.

Open source node based multi-media mega interface activate!

Sitting on the floor of my room with equipment and cables spread out I used to dream of owning a modular synth. If you had told me I could have one on a booklet thin laptop computer, I would have cried.

It's node based, as it should be!

Flash based modular synth!
http://petervandernoord.nl/blog/