I like vectors, and that was what I tried origionally. The PROBLEM is that it takes an ungodly amount of time to make something good. I went back and forth trying to blend vector with non vector, and basically the conclusion I came to is this. Single layer is the best, fastest and easiest to blend, but its a bitch if you change your mind about something. Vector lets you reuse stuff to your hearts content, and scale objects as much as you like, which is in theory nice, but I often times ran into issues trying to rescale vectors and had to do quite a bit of modification.
So what I ended up doing is just working in high resolution with the assumption of scaling down (no loss in quality in final result) to gain the sharpness, and detail I want, ditch vectors as an element, but I do still use them to mask, and in areas where mouse is just too damn hard to get good lines, but at the end of the day, EVEN WITH MOUSE AND KEYBOARD, it just never looks as good, and is never as fast as what you can do freehand. So I have chopped up the pic into many many small segments, the same way you would with flash, but I am doing it in a way that tends to look a lot better than flash, because the elements aren't designed to be animated, just modified, and I can very quickly iterate on things. I also over many experiments found clever ways to not need vectors the way I originally thought I would to do many things, like recolor, and once I have a good mask, I can do a simple color and palette swaps and a lot more really than I would have expected. If you are working on doing similar things, I can share the PDS file. IMHO the biggest issue is just getting some baseline stuff created, and once you have a decent library, it wouldn't be hard to make "randomly generated" characters, even if it is done by hand in essence, it lets you make a really large pool very quickly. That was my intention initially, was to make a basic character set for one character, and then see how long it takes me, or how many elements are reusable on the next. I suspect actually that a lot will carry over. I will likely have to completely make different body types such as thin, fat, athletic, and possibly tall, short, adult ect, but having a handcrafted look just looks way way better overall, and I always appreciated that hand drawn look over things that look overly CG.