For a hand drawing one giving tons of control over stroke settings, and evolving, is MyPaint . Scribus , a layout/publishing tool, is told to be one of the very few supporting well CMYK. Indeed, some people do their design in Inkscape, and export to Scribus, so they do there the cmyk stuff, etc. And believe it or not, I have used Blender from time to time as a helper in some graphic work (rarely for a design)
Was forgetting sk1 , cmyk, etc support, an illustration tool supposedly better suited for print. It might be yet a work in process and maybe not in all platforms, yet (only linuxes at the time of writting this answer, next two releases will bring Windows and OSX versions). I'd keep an eye on it. : http://sk1project.org