I've seen a few requests of people in the discord to essentially clear their favorites. E621 does not provide this feature by default, but it is automatable thanks to the API.
I made a small page on my site where you can do this, and it also allows for filtering what you will be unfavoriting. The filter syntax is identical to my advanced search syntax, however it does not support metatags.
You can find the page here. If you are using this, I highly recommend using the first button first which will show you all the posts you will be unfavoriting. This is so you can ensure that the filter is working.
The API does have a rate limit, so the more you need to unfavorite, the longer you will need to keep the page open. It will tell you how long the process will take and alert you when it is finished. The page is very simple, so do not expect fancy UI.
The code behind this can be found with the rest of the site, at its github, here
Let me know if you run into any issues, my limited testing seemed to work.