Just a hunch, but when you pedal, does your butt rock from side to side? It shouldn't. That can be caused by a saddle that's too high (unlikely if you're riding a comfort bike), or just out of habit. Keep your butt steady and pedal from the hips down.

You mentioned you use a mix of mtn and road shorts. I assume you mean dedicated shorts with built-in chamois. Don't wear anything under your shorts.

Any lotion applied to that area just prior to riding will help, some work better than others. You can buy products specifically intended for that (see slowandsteady's post... personally I don't care for petroleum jelly & bag balm, it's a little too persistant, particularly in the shorts). I normally don't need it, but have had good luck with something called Udderly Smooth Udder Creme, available from the local Wal-Mart.

Saddle can definitely be a factor, as well as saddle tilt and height. For example, I require a saddle with a narrow nose so my thighs don't rub against it. Likewise having the nose tilted up too much (which can also cause other types of discomfort).

Finally, when I had trouble with chafing, I found that it was pretty slow to heal and easy to re-irritate. Even if you solve the problem, it might take a period of reduced mileage to actually improve. Good luck and keep working on those new tricks.