You gotta think big.
Plan a region with at least seven connected cities, one being central.
Outsource garbage, power, and water to individual radial cities so as to isolate the majority of the population from the negative effects of said resources.
Route the buying and selling of all resources through the central city. This simplifies the region’s economic network and minimizes the chance your head will explode. Example: Electricity City sells electricity to Central City, Central City sells electricity to every other city, Central City buys garbage from all cities except Garbage City and then sells all garbage to Garbage City and so on…
My favorite grid network uses 5x4 zones which are alternately separated by 1 and then 3 spaces. So, zone, road, zone, road, space, road, zone, road, zone, etc… All roads are one-way. This optimally balances pop density, traffic congestion, building height/size limits, and creates space for bus stops, parks, subway stations, trees, etc…
Once you have the grid structure established, use it modularly. Don’t be ripping up streets and re-laying them when changing zone types. Just leave the grid alone and rezone types as needed while the city expands.
As for gifts/rewards , plop them as soon as you can, and don’t be afraid to smash them and re-plop them to suit your growing population. These buildings are very powerful and must be considered with/against each other in terms of synergy. Some are res+ but com neutral, some are + all around. Some are com+ but res -, etc… Also, some have a dramatic radius of effect, so consider that as well. When placing a reward, do not alter your grid to accommodate it. Just plop the damn thing and rebuild the grid if/when you move the reward later. This will let you maintain the modularity of your grid structure.
At the very beginning, start with you central city. Spam some residential and place one fire station. Tweak it until it generates a profit. Let it run for ages, until you have, say, 4 million dollars (simoleons?). Then, smash the feeble little town and get to the REAL work. This will give you some breathing room. Although you will still need to watch your +/-, you should be able to avoid the dreaded loan spiral. Nothing will crush you like a loan spiral.
Of police, fire, health, education, etc… I’d say education is the hardest to manage properly. It requires the most thought and tweaking. Stay on top of it. This goes a long way towards having a region awash in hi-tech industry, an essential quality.
Ensure that every city in your region is generating a profit. If you have a radial resource city that is losing cash, don’t leave it alone and work on something else! Work on that city until it generates a profit. One single, neglected city budget can crash an entire region. All cities, all profit, all the time. Pay special attention to the relationship between your Electric City and your Central City. This relationship is the cornerstone for the entire region. If it fails, bye-bye region.
With outsourced resources you can fill an entire large city tile with successful, booming high density res and com. Any ind still in the main city will (should) be hi-tech. The cities surrounding your central city will be loaded with hi-tech that is driven by and supported by your main city.
By this time, your region will be an efficient, clean juggernaut and your computer will be so bogged down in sim goodliness that it will take ages to load any one city and you will decide that you have won and you will quit.