It seriously depends on several different things, #1 being what you like the best as far as style and workflow are concerned. It also depends on what program you're working with as well.
For actual painting & drawing, I've found the best program to use is Corel Painter, but Photoshop has many of the same features for changing all the shapes/dynamics/spacing/etc of brushes, where Corel Painter has many more natural feeling brushes, with specific functions for different types of art such as water colour - in Corel Painter, water colour is dealt with in it's own layer seperate from the rest of the image....you would normally create a new layer for this type of thing in Photoshop anyway, but the dynamics are slightly different, as Corel Painter takes in consideration for things like "bleeding" and "smearing" with the water colour.
If you're not dealing strictly with hand drawn stuff in Photoshop, you can create a layer of "render clouds" through one of it's filters, throw in an alpha channel, and modify it to the image settings, which is much easier than it sounds (for the noobs).
Still, it's hard to say what approach would be best, since you could be using a program different to the ones I've mentioned, like GIMP or Paint.NET, or some other free program available.
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