The techniques I use to create images in Adobe Photoshop have been evolving towards a more traditional style of painting.
Moving away from using masks and heavily layered files, to directly painting onto a handful of layers, has resulted in a more creative process.
Some artists will prefer painting into a palette of spot colors to be used in the printing process. This approach is great when creating simple color blends, or if you have mastered the process of painting a color separation.
For myself, I prefer to create an image according to my preference, and separate colors as needed for the printing process. So while I am considering the printing process while painting, I am not always limiting myself to the number of colors used in printing. In practice this means painting an image in the RGB color mode, and using color separation techniques to reproduce the image on press.