I use Adobe Photoshop CC for all of my drawing, and Shoebox for putting together sprite sheets.
If I need something done in multiple perspectives but am having trouble drawing it out, I'll create the basic shape of the object in blender first, then render out 2d images from different angles as a working reference.
My background is in three-dimensional design (as well as fine arts), so sculpting something out or doing lots of rough sketches in a sketchbook is my starting point