I want to chip in recently from personal recent experiences.
I used to use Paint.NET, Inkscape, Gimp a lot. Free. Good enough most of the time. However I have to say recently I bought a cheap Wacom tablet and found that Paint/Gimp just kinda suck for tablets. So I was suggest to try Manga Studio 5 because PhotoShop is expensive(I don't pay monthly for tools).
WOW. I tried the demo and wow. The tool is far more intuitive. Faster. More effecient on the CPU, the tools are far better laid out than Gimp/Pain.net. Also MS5 has Vector Layers. So you can mix and match your art. Though the Vector work is a little less than InkScape. That because Vector art in MS is for inking mostly. It was just outstandling better than Paint.net/gimp. I was surprised.
Also I got MS for super cheap. I really suggest anyone who is going to do digital art work to pick up one. If you can't affort PS like me. MS is a fantastic vastly cheaper alternative that's far better than the Gimp/Pain.net. http://www.amazon.com/Smith-Micro-Softw ... angastudio http://www.amazon.com/Smith-Micro-Softw ... angastudio