TwoSix
Everyone's literal second-favorite poster
I think they certainly can work, but the best approach would be to build the class system around the expectation that they'll exist. More of a 5e overhaul than a 5e add-on. Have more generic, low-magic class options available at 1 that only have somewhere between 5-6 levels of progression (with a mini-capstone), then a whole suite of prestige class options that are linked to campaign concepts and provide your stronger, higher level abilities.