I use Jasc Paint Shop Pro. You can find a trial version (usually around 7.00) on oldversion.com to test out... and the Interwebz can probably find you a cracked version...
If you were doing a high-res game you will need large sprites, that the engine would shrink. Shrinking makes them lose detail but you can be clever and only use that feature for dramatic effects such as to show how massively large something else is. Zooming in is also good for dramatics.
If you're spriting a Belmont, they are usually 45 pixels tall, and are usually taking about 24 pixels in width You can use that as your frame window. Later on when you do animations, if the animations take up a lot of wide space you might have to take more width pixels. I usually use a squared frame, about 64x64. That's good for most animations unless they get ridiculously complicated.
If you're doing High-Res, you might be better off with a larger frame size, like how they do with fighting game sprites.
Lastly, you can use CAD or AI to make vector art. A good way to use vector art is to set up a marionette-style animation, where the joints are cleverly overlapped. This will generate a game that resembles Odin Sphere or Muramasa.
As you probably know, if you use CAD or AI for Vector Art, you don't need a pixel size, just a relative frame window that stays consistent.