People have certainly built Cities: Skylines cities with mixed-use developments, quaint mountain towns, little enclaves built around a park or monument, car-less cities, pedestrian-only cities, modular cities connected by mass transit, etc.
I think the problem - in SimCity, Cities: Skylines, other video games, and real life - is that if you're building for aesthetics, there are many right answers, but if you're building for efficiency, there's only one right answer. The reason so many mid-size American cities have converged upon 1/4 acre lots with a road hierarchy, 3-lane boulevards, commercial strip malls on the boulevards, office parks, and freeways to link suburbs is that that's the most efficient way to satisfy the constraints of 2-3 child nuclear families who want privacy and a patch of greenery that's all their own and have varied destinations that each support too little traffic to be worth building mass transit to. The reason many megacities (I'm thinking particularly of NYC + Asian megacities like Beijing, Taipei, Hong Kong, Shanghai, etc.) have converged upon high-rise condominiums with street-level retail taking up whole city blocks with abundant bus & mass transit routes is because at a certain population density the suburban model ceases to work, and this becomes the only feasible way to move people to work & shopping. Interestingly, both models show up in Cities: Skylines, and the transition point between them is usually a painful inflection point in your city's development.