Once (and I emphasize ONCE) I took a longish (54 mi?) ride in my normal undies. The style I buy has a big lump of a seam right in the leg elastic which is, incidently, right where my butt meets the side of the saddle. DH had to put moleskin on my behind the next day before I could ride again. I don't think I had any skin left. As it was a tour, I had to keep going. He will probably never let me forget.

So, yeah, leave the undies at home.

And now I ride a recumbent, with a whole new host of issues, but no more moleskin on sensitive areas for me.