So I was having a shifting problem with the rear der (Shimano RD 6800). I tried to adjust it with the barrel adjuster but if it shifted up smoothly it wouldn't shift down and vice versa. This was only happening on the smaller cogs and I could even get it to hesitate on both up shifting and down shifting at the same point of adjustment. The larger cogs on the cassette are not having this problem. So I replaced both the cable and cable housing and am still having the same issue. I released the cable at the derailleur and manually pulled the cable back and forth thru each component of the cable's run and there didn't seem to be any tight spots. Any ideas?

How old are the cassette and chain?

Are you sure the shifter was set correctly when you attached the cable (highest gear setting)?

Also, set the chain on smallest cog and big ring and eyeball the derailleur cage.

— Is it lined up directly under the cog? (if not, adjust H limit screw).
— Is it perfectly vertical? (if not, bent derailleur hangar)

Being able to shift up not down or vice versa often indicates excess cable friction.
Since you have replaced the cable and housing (you did replace ALL of the housing runs, right?) then the next thing I would check would be the derailleur and hanger for straightness, and the derailleur for excess friction.

cassette < 2000 miles, chain < 500 miles, shifter was set correctly, but to my eye, derailleur does not appear vertical, so looks like a trip to the LBS for hanger alignment check. Thanks for your time and advice; I'll let you know what they say.

Have you had the derailleur hanger alignment checked?

Whenever I encounter a rear shifting problem that doesn't respond to normal tuning that's the first thing I check. Most times - that's it.

Other things to check are:
*Cable attachment point, there's an arrow to mark if it goes on the inside or outside of the bolt. For the RD-6800 the SS (short cage) it's inside, for the GS (long) it's outside.
*Also cable adjuster at RD. These have an additional part inside the adjuster, not just the barrel and spring as in prior RDs. Not sure if these clog/wear.

I've grown protective of the derailler hanger. If leaning the bike against something, the hanger faces away from a fall. This precaution due to a bent hanger from merely loading the bike, hanger side down, into my car.

It may not help your situation but I also douse the shifters, from time to time, maybe once a year, with a lubricant. In my case, Slick 50, so that it runs out. It is a bit messy for several days but those shifters are quiet and reliable

Turns out it was a bent hanger. Thanks again for the help everyone.

It turns out this way SO OFTEN that I think a good rule of thumb is this: if you don't KNOW for a fact that the hanger is straight relative to your frame* then the first thing to do is check the hanger, and adjust if needed, with the proper tool.

*Even a brand new hanger may not be straight relative to your frame, so the only way to guarantee a straight hanger is to check it.