Mac: We're huge fans of Notational Velocity as a syncing note-taker, and nvALT beefs it up even more with things like a widescreen-optimised view, custom colour schemes, a menu bar-only mode and lots more.
Notational Velocity, on its own, excels in simplicity. It's one of the reasons we like Simplenote and Notational Velocity so much. However, if you live your life in Simplenote -- that is, actually doing lots of writing rather than just jotting down notes once in a while -- nvALT is an alternative version of the app that brings in a stack of great features.
When you start it up, it looks exactly like Notational Velocity, but you can tweak it very heavily to fit your needs. It has a widescreen view similar to Simplenote's web interface, which is great for seeing more of what you're writing, plus a full screen view for when you really need to get things done. It also has a low-contrast colour scheme as well as the ability to customise your own. It even supports stripping out extra junk with Readability, Simplenote tag sync, and extra keyboard shortcuts. If you're at all a fan of Notational Velocity, check out its full feature list to see everything nvALT can do.
nvALT is a free download for Mac OS X only.