You could try avoiding states with three vowels in the name. Not because they are inherently unsafe or unpleasant, but more because it might make for a more intriguing route . Bonus points for avoiding counties whose vowels come in consecutive order.

I've cycled in all 50 states and wouldn't put anything in the "avoid at all costs" category. For me it has been much more situation-dependent where I occasionally got onto a very busy road in midst of road construction, etc and not something as predictable as blacklisting a state or city.