It depends on how much effort you put into the midi transcription, but a trained musician could probably still tell the difference, especially during the transitions in between notes, and certain dynamics. Some sample libraries go as far as to record entire phrases played by a musician but then you're limited to what musical phrases those recordings include and how they were played (pitch shifting has gotten very good, but let's say you want a violin melody to sound softer, or plucked instead of bowed).

Instruments where notes/hits are isolated from other notes/hits like a piano or drumkit work wonderfully with sample libraries. But things like a guitar, violin, or trombone are still challenges. Even the orchestral libraries that are hundreds of gigs and thousands of dollars don't get it perfectly on their own. You definitely can make recordings that trick a trained musician, but not without tons of effort customizing your midi transcription to that specific sample library and you may have to compromise and avoid certain techniques that still don't translate to sampling well.

This is just talking about trained musicians though. Taking a midi transcription of something, spending 10 minutes adjusting velocity, and then loading up some EastWest samples would probably fool the average person.

Also quick edit but many people would consider something using samples of recorded instruments to still be a midi synthesizer because you're synthesizing a performance from samples, as opposed to recording entire phrases or even longer sections with a real musician and then arranging samples to create a recording. Not everyone would agree, but I'd guess the original commenter also had sample software in mind along with more traditional electronic synthesizers.

Even on a piano, two notes that are played independently, then later mixed, sound different than if those same two notes are played together on the piano. Something to do with the sound from one note affecting the string vibrations on the second note, and vice versa.

Very true, me saying they're totally isolated isn't 100% correct. That's sympathetic resonance, and other details like the pedals also slightly affects the resonance and pressing the pedals may be audible in a quiet/intimate recording. It's very subtle though and probably not noticeable by anyone who doesn't have lots of experience with a real piano. Many modern piano libraries actually do model/sample those properties though (I have no idea how).

While we're on it, drums aren't totally isolated either, they affect themselves. A snare roll is slightly different than just playing many snare samples rapidly because of the chains on the drum, and heavy cymbals also take some time to build up momentum so the first hit and tenth hit will sound different if it has not settled. These are all very subtle though compared to something like a guitar or violin or trombone where transitioning from one note sample to another sample digitally can be very obvious.

On the topic of how those modern libraries manage to reproduce those effects, couldn’t they have used either pure bruteforce (i.e., recording and sampling every combination of notes hit together) or some advanced modeling of physical properties of pianos to recreate how the sounds coming from piano strings would interact simultaneously? Or even better, some combination of those two approaches (modeling and extensive sampling)?

Disclaimer: i by no means have any expertise on the topic and am just as curious about figuring out how it actually works as the parent comment.