System Information
Operating system: Darwin-18.7.0-x86_64-i386-64bit 64 Bits
Graphics card: AMD Radeon Pro Vega 64 OpenGL Engine ATI Technologies Inc. 4.1 ATI-2.11.21

Blender Version
Broken: version: 2.81 (sub 16), branch: master, commit date: 2019-11-05 18:23, hash: rB9d1031b01199
Worked: (optional)

Short description of error
Adding a Reference Image to a Collection and making an instance of that Collection works as expected.
But adding additional objects to that same Collection will cause the instance of the reference Image to draw at the wrong size.
Furthermore this scenario seems to make Blender unstable such that the Magnifier Glass, Hand, Camera and Persp/Ortho buttons draw as black circles and all of the reference images vanish entirely until Blender is restarted.

Please note that I've gotten into the unstable state8 or 10 times now, but I can't quite pinpoint the exact series of steps that cause it to happen. However, the first part of the glitch where the Reference Image breaks in an Instanced Collection is reproducible easily on my system.

Exact steps for others to reproduce the error

Open the blend file ref_glitch.blend
Notice how the Reference Image in the Collection is the wrong size.

From a New-> General file...
Delete all 3 default objects.
Add->Image->Reference
M key to Move the Reference Image to a New Collection called "ref"
Add Collection Instance->"ref"
Add Empty Object.
M key to Move the Empty Object to "ref"
Notice how the Instanced Reference Image now draws at the wrong size.
Delete the Empty Object.
Notice how the Reference Image draws at the correct size again.