The big downside is making payments on sites with silly amounts of 3rd parties involved
As a user of NoScript for many years, the easiest way to deal with this for me is to do my payments from a second browser. I have found LibreWolf to be really good as far as not blocking what it takes to do such a transaction but still blocking everything else very well.
I don’t like to use NoScript under purchasing/payment circumstances; multiple sites are often involved in payment processing and it’s too easy to break what I didn’t know was there under my usually very strict rules.
Sure, I could just turn off NoScript for a site I want to do a financial transaction on, but instead of dicking around with it anymore I just use a different browser because the upsides are so good.
Like online shopping: I shop on one browser, and login and pay on another, which also allows me to strip any unwanted affiliate links and tracking information from the URL when I do purchase something. I also get to see price differences between anonymous and logged in users, which is another game online retailers like to pay: logged off there is a low bait price, and logged in switches you to a higher price (Amazon does this by changing the recommended seller of an item; I just log in on the second browser and change it back, lol).
Any different browser with NoScript turned off and secondary blocking (uBlockOrigin, uMatrix, etc) enabled will serve the purpose, if you’re not interested in a puzzle one day.