They are effectively becoming the new $20 with inflation continuing upwards, and I expect their popularity to continue to increase.
Let me introduce you to a $2 note.
https://en.wikipedia.org/wiki/United_States_five-hundred-dol...
https://en.wikipedia.org/wiki/United_States_one-thousand-dol...
https://en.wikipedia.org/wiki/United_States_five-thousand-do...
https://en.wikipedia.org/wiki/United_States_ten-thousand-dol...
Your best bet of happening into a $50 is if you go to a bank for an in-person withdraw and they ask you for preferred denominations. Generally the money is dispensed in $20s even there unless specified.
Your second best bet would be if you're selling something "on the side" and the purchaser uses a $50 in a transaction, which I would say is also rare these days, most people use Venmo or equiv.
Your best bet of handling a $50 is probably as a bartender, or of course as a bank teller.
I have held $50s a few times in my life, and even my reaction is "huh, a $50, don't see those often"
Nowadays that's less common from tourists from Europe, but tourists from Asia are still likely to bring cash.