Is it so weird that I love using Photoshop/Imageready for animating sprites?
I received a lot of strange responses at an indie developer meet recently because of this. I've never had any problems with it though, and I'm pretty excited about getting CS4 at work some time in the future, as it has some cool new animation features.
I use PC and Mac (PC laptop, PC at work, and Mac as main desktop PC), so being cross-platform suits me too.
Pixen is pretty much unusable, IMO. It has too many faults, it's really not practical to use. Don't do it, kids!
You could probably use Graphics Gale via VMware Fusion though (especially in Unity mode), if you wanted to use something other than Photoshop on a mac.