There absolutely is a reason. Microsoft's reason. Scaring users away from independent software distribution means more people will use the Windows Store.
The strategy is to introduce the store and slowly make independent distribution more and more onerous, using security as justification. When people complain you can say "just put your app in the store and you won't need to worry about signin/notarisation/etc."
Apple are doing exactly the same thing.
I have never seen a regular computer user not clicking the "Run" button in less time than it takes to read anything in that window. One notable exception I can see is people who've pirated games from gog.com, and want to check that they're unmodified.