I’ve been using both for a while, and I’d give the biscuit to Substance over Quixel any day.
Quixel has lots of really intuitive features, but the fact of the matter is it’s buggy as sin. This isn’t just my experience either, everybody in the studio that’s used it has cursed it’s name with the force of suns at least a few times this year. It’s a great toolset if you want fast results, and if it doesn’t crash. I also find that 3DO doesn’t give you a decent preview of how things will actually look in game.
Substance is more difficult to use and could do with some more features, but ultimately more rewarding because it’s virtually limitless in terms of what you can create. Quixel is still pretty limited by it’s pre-set materials system, which you can modify and create ones of your own, but it’s just not an intuitive process. I’ve found that it’s materials are just the same sort of generic things you’ll find in any game. If you want to push the boat out a bit and explore, Quixel probably isn’t for you.
Both are good bits of software, but I’m glad I’m not the one who bought my Quixel license. It’s current state is that it’s far too buggy to consider in a real pipeline. I’ve lost a lot of hours of work over the year. It just feels messy.
So yah, if you can put the time aside to learn more about Painter and Designer, it’s definitely worth it!