I don't think there's a perfect solution, but of the popular systems I've seen thrown around, I do think the customizable pop-up (i.e. off, auto, prompt me per reaction ability) is probably the best one. Anyone who really is bothered by it can just set it to "auto" or "off". Maybe if Larian is ambitious enough they can also give "auto" some logic/planning, but that's basically a dream right now.
There are some abilities that probably needs to be changed from 5E RAW to work with even the "customizable pop-up" system - i.e. the Diviner's Portent ability (which lets you affect ANY roll you can see, friends or foe) will trigger WAY too many pop-ups for even my taste.
The "QTE" system I've heard people talk about (i.e. interrupting things like in real Table Top) has potential, but in my experience I've never seen a happy marriage when bringing real time and turnbase mechanics together. However, I'd take it over only have the option to go automatic reactions.