I've been tinkering with a new Wacom tablet over the past few weeks (as evidenced by the sketches in my photo stream). The hardware would be nothing without software, so I've also been playing with ArtRage and Project Dogwaffle. For UI and simplicity, it's 'Rage all the way. For advanced tools and unique brushes, go with the 'Waffle. I've never appreciated the latter's “doggy” interface, but 3.1a adds a spline based paint engine (aka, Penny). Pretty freakin' sweet, as my friend Peter Griffin would say. I wasn't ready to get a full-fledged Tablet PC just to play with a stylus on my screen.
If I'm feeling stressed, I can just pick up a virtual pencil and start drawing random objects – like caricatures of friends and family members! PD Pro Digital Painter is always there for me, although I know I'm not taking full advantage of what the program has to offer. You can play with v1.2 for free, BTW.