I've been tempted by MLS many times but yeah.... the rules are just so different from anything else in the footballing world that they never seem to get them functioning quite right.
South America in general is fun, but Brazil is honestly the most fun I've had. Like any save, its going to vary somewhat based on the size of club. I usually run with Atletico Mineiro and they are quite big. Santos are an interesting proposition - despite the recognition they have globally from the Pele era, they really haven't had huge amounts of success. They have 3 Copa Libertadores titles but 2 of those are from the 60s. They have 8 Serie A titles... but 6 are from the 60s and the other 2 are almost 20 years ago now. they are not among the biggest clubs in Brazil by most measure. They do have 22 Paulist state league titles but those mean less, especially today. So building them into a true giant of Brazilian futbol would be an interesting project .
Santos do have one of the better youth systems in Brazil - so therefore the whole world. They have a lot of promising players in house already and tend to get 4-star prospects every year, with a 5 star often enough.
I've said this before, but.... Brazil is just flat out fun. If you have a decent club reputation and some money, you can just load up endlessly. Every player in Brazil had a release clause for domestic clubs and for youth contracts, its tied to their wage. so newly generated newgens are usually 275K to poach. So you sell a 20 year old wonderkid to Europe for 10m and you can buy up enough 4 and 5 star newgens to fill two squads. There are enough of them generated that you can be picky and select ones that suit your play style. You are having to constantly load up and rebuild because any players who stand out will be wanted by Europe and elsewhere. I like having Mexico and China as active leagues as they will be constant suitors.
Other nice things about Brazil - the state league can provide an easy trophy every year, depending on the club and the state. It also provides competitive matches for young players to gain valuable experience. The fixture congestion is intense and you rotate a lot. Lots of amazing coaches to hire. And the foreign player restrictions are more open than most leagues in South America so its easier to poach the best of the youngsters from elsewhere.
I'm still rolling with Argentinos Juniors but I don't know how much longer. it might take getting a really nice newgen in the first intake to keep me invested.