Bumping and updating - the post is not correctly titled. I don't think it's directly related to the HiDPI mode (it's just that using the 'ignore' settings corrects the issue, because Reaper isn't scaling with the OS on these settings), it's an issue that occurs when using two monitors at different scaling settings.
I have found a free VSTi that exhibits this behaviour, in the hope that the Devs or someone else can test this and confirm it.
https://decomposer.de/sitala/
Steps to recreate -
Run two displays at different scaling settings
Open sitala in Reaper and try to click the buttons when placed on either display - they will only work correctly on one of the displays.
Thanks.