I have been playing skyrim since release date and only cleared my system and game cache once after second patch if I remember right. Since then; I have played over a thousand hours on numerous characters and have downloaded all dlc and occasionally encountered glitches or npc's acting strange or erratic, but nothing game breaking. Over time, when an npc did something different I always assumed it was do to last patch or something in new dlc:
Some examples:
-Npc's not finishing dialogue as I remembered or major pauses or lapses in speech patterns
-npc's having trouble walking to where they normally go or not even walking to where they normally go but eventually being loaded wherever they were finally intended
-full animation sequences of npc interaction not loading
-random items falling on floor (became more apparent over months and months of play) - I always cleaned up,etc...
-arrows increasingly misfiring - only going a short distance
- just overall generally glitchy

Like I said - none of these affected the continuing of quests or gameplay so I just assumed it was stuff being addressed in patches or new dlc and would eventually be fixed

So - today I started another new character and noticed some minor npc variances from memory and so I said what the heck and started completely over - I erased all game saves which even included level 81 characters - I then preceded to clear system cache and game cache - I did not delete installed game on hard drive nor any downloaded dlc

I then started a brand new game and could not believe the difference in performance and npc interaction - huge difference immediately noticeable

So - I would recommend this to anyone who has not done it in a long time

Obviously my system or game cache was slightly corrupted

how do you delete system and game cache?

You shouldn't actually have to delete your game saves, just clear the cache and delete/reinstall the game data.

(this for others, obviously, since you've already done it.)