Typically used Mockingbird/Balsamiq, but I'm now leaning towards something that can double for rapid prototyping – i.e. interactivity can be added to the wireframe – which puts me in Axure/Hot Gloo territory, about which I know very little.
I've used Balsamiq and it works for lower fidelity stuff but I just got pissed off with the AIR implementation and the lack of finer detail if you wanted.
Omnigraffle and the konigi stencil set work really well and you can go as high/low fi as you want. It also exports direct to HTML so you can test with clickable wireframes too. It now supports all the new Lion features too.