Personally I really hate inefficiency and there for I've been struggling to build the most efficient setup, However I feel like I've come to a point where I can say I actually found the way!
You don't want your conolists to walk great lengths towards work, yet don't have too many roads.
Looking at the posts already made on the forum I'm in love with the arcology setup and used that as a base template, I have yet to do the math on the best population to work ratio but so far all is looking good.
The 'Arcology setup' is a great start and my favorite way of building. However the 8x8 squares do not offer the most efficient way of building. By using rectangles of 8x21 this efficiency is increased. 1x1 2x2 and 2x3 setups.
Please forgive me for mismatching the blocks in the picture.
I personally built my latest city by handeling horizontal roads in repeated blocks of 8 4 8 and (depending on building sizes) vertical blocks of 8 4 8 for housing and essentials and then blocks of 21 / 16 for different size buildings.
Building with 3x4 and 4x3 however are somewhat less efficient in this setup. By simply building them in blocks of 3x2 and 2x2. Buildings that have larger sizes could be placed at the edges as separation of the buildings that do not need workers.
Maby a picture would make more sense then all I've been saying..
I know I'm missing some details in this post, note that it has to be worked out some more :) anyways pictures said enough I belive