Seams and the edge of the chamois can abrade skin pretty badly.
I have some very good, top-of-the-line Sugoi shorts that worked well for two seasons and then started chafing badly last season. The culprit is the chamois edge, which is quite prominant and I presume it has now hardened enough to cause problems.
Certain saddles will cause issues depending on where parts of them line up with different shorts. Carry spare shorts and change every 200k or so. Also carry baby wipes and keep clean.
I use Body Glide for lubrication.