What do you use?
Illustrator has one real advantage over most of the competitors, in as much as all your strokes remain individual editable elements.
However, I've got a 2.16GHz Core 2 Duo iMac with 2Gb of RAM and a passable graphics card and I have serious performance issues with my graphics tablet with Illustrator CS3 (and with Photoshop CS3 too). I'm given to believe that this is due to Adobe's shitty coding, a suggestion supported by the fact that I have no such issues in with non-Adobe software!
Manga Studio (the virtues of which have recently been extolled by no less than Dave Gibbons) comes in two flavours, Debut and EX. As I've said previously, I'm only interested in Manga Studio for inking (although I think I could probably get used to pencilling, too -- there's a perspective grid feature that's very nice) and so I don't miss any of the features that are restricted to the EX version.
The Debut version costs $49 and can be downloaded directly
here.
Limited version or not, I feel like I'm really only scratching the surface so far, and the (seemingly) unlimited number of Undos goes some way to compensating for the lack of editable strokes.
I've tried to get to grips with about three different versions of Painter over the last ten years, including one attempt last year, mainly because the pens actually behave like pens. However, the interface has always been horrible, and remains so as far as I can tell.
If I could get Photoshop to behave itself, I'd be tempted to do more work in it, but for right now it's too much of a pain to attempt any significant kind of drawing work.
Cheers
Jim