It describes in part how some volunteer brain scans are actually quite agreeable to work with until they work for too many hours, and then they get fussy, but it's cool, you can always reboot them. But you need to hide from them the fact that it's been decades since they were scanned and uploaded, or they'll realize how long they've been slaves for.
For every episode except the last 1-2 the characters are not textually aware that they're simulated humans made from a brain scan, and the conflict and plot are largely interpersonal conflict and being forced into adventures by the mad AI that runs the simulation. The characters wish that they could leave and/or change the simulation, and eventually accept their situation, and part of the conclusion is the idea that it's worth existing in their limited simulation and trying to make the best of it even though they'll never leave.
You could say it's exploring what it would be like to be trapped in a simulation with a mad AI, but I wouldn't say it explores the concept of ethics of simulating humans in general. Most of the things the humans don't like are arbitrary limitations of this simulation in particular (can't talk to the outside world, can't choose your form, can't have sex, can't have any impact on the world, forced into zany situations by an AI that doesn't really understand humans or listen to them), not anything about simulations in general. The finale touches on the idea of the simulated humans wondering about their original versions and what they're like and what they're up to, but that's about it.
Basically, I don't feel by watching the show I encountered any non-trivial ideas about human simulations just because it's about a simulation.
But "The Amazing Digital Circus" explores this concept relating to human brain scans, and how the 'simulated' brains would react under simulation.