Good question. There’s always a little spark of delight that flares inside me every time I find a playable in-game instrument.
I think my first encounter with something like this was in Ocarina of Time. I feel pretty confident saying everyone who has played that game for a decent chunk of time has tried to make some ghastly noise on the ocarina. Wind Waker had this too, with the titular instrument, in a more limited capacity.
Overwatch has bells on the “Dorado” map spawn area that you can play by shooting them. I think there are 3-4 different notes there. Not much but it’s neat.
I remember a part in Super Mario RPG where you could arrange tadpoles on a musical staff to make a short melody for a composer named Toadofsky (hmmm…). Not technically an instrument but it’s way more musically in-depth than a lot of games go.
I also feel like I’ve played a game, maybe a JRPG, with a floor piano. I’ll edit it in if I can jog my memory