Gooood day, ladies and digital-men!
I'm planning a game set in a large-scale "sandbox-style" city with roads and buildings and everything in-between (except the kitchen sink...that might break the game...all that plumbing...).
There will be very little changing of layouts - ultimately, I want the game to take place in one giant city. (Although, literally as I was just typing that, an idea occurred to me on how I could change layouts and yet still keep the semblance of a large city...more on that later.)
My #1 concern is CPU/GPU overhead. Obviously, the more the computer has to compute, the more bogged down it's going to potentially get. 
Ashley & Co have been working miracles and wonders to make everything work as efficiently as possible so my concerns may not be all that warranted as they might have been had I tried this game on, say, C2. Still, I think it's important for me to begin keeping this detail amongst the top of my priorities.
Here are some things I know of or I think I know of that will help to keep CPU usage down...
- Keep related objects in folders. Objects that are directly associated with each other (ie: containers, objects pinned to another, etc) should all go into a folder. For reasons I cannot articulate, this just makes it easier for the computer to reference, drawn, manipulate, whatever every tick.
- When dealing with road objects, specifically long road sections, having the road pieces stretch via height or length will obviously reduce the number of objects needed to be drawn on-screen (and less to track overall). I am, however, unaware of the use of a 9patch vs sprite vs tiled background will be of any benefit in terms of CPU usage.
- Effects, WebGL, particle objects, etc, tend to be a bit more demanding on CPU/GPU. I should use these sparingly, even with the improvements to C3 runtime. ...... At least, this is my understanding. I fully welcome correction.
- Objects off-screen are not readily drawn. So I don't need to tell C3 to draw objects as invisible when off-screen because they're literally NOT drawn given that you can't even see them anyway.
That's all that comes to mind at the moment.
Any and all suggestions would be greatly appreciated.
Also, please go easy on me on technical jargon. I've been using C3 for a while, but some of the terms and such for more "professional" level of game design is still rather foreign to me. I may need to ask questions for clarification in order to make sure I know I understand what you're explaining.
Also, my friend, 
SycrosD4, is teaming up with me and is very new to C3. He'll be handling the art-side of things and I'm sure he'll appreciate the info, too.
Thank you everyone for your help and input!