We've all seen those chemicals on the shelves, screaming at us "HEY, I'LL SAVE YOU TONS OF MPG FOR $3.99, I SWEAR ON MY GRAMMY-MA'S GRAVE MAN, HEY WHERE YOU GOINGASDGASHASDFASD" It's what it sounded like, anyways (-)
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We all also have probably had the urge to buy those bottles. Ever wonder how they REALLY work?
(Belongs to http://automoblog.net)
In your fuel system, carbon builds up over time. This restricts fuel getting through and may place more wear on components like the fuel pump, kind of self-explanatory on what it's job is. This cleaner will pass through the entire system, along with the gas, and help loosen those carbons deposits, sending it through the intake valves and shot out the outtake into your catalytic converter. It also may clean the piston, too, as it gets shot into the cylinder and gets compressed with the air/fuel mix.
The only bottles of that stuff I buy is maybe an occasional fuel system cleaner and I trust Heet to keep my gas flowing and last longer over the winter. No, I was not paid by them, I am just sharing my opinion about how good their brand is.
Now that that's out of the way. Second section: Tires, tires, tires!
Low rolling resistance is a good key factor to add in, as the more rolling resistance you have, the more it takes for the car to roll the wheel. connecting the dots yet, buddy? Many things can add in to resistance such as design of the tire itself, your car's alignment, or the current condition of the wheel hub.
If your car's steering wheel isn't completely straight when going down a straight line, that may be hurting your mileage by having two tires roll towards each other too far. Ever try to load down a shopping cart with a stuck wheel? Imagine your car pushing 1.25 tons with that.
Part Three: Driving Habits
This is the biggest blunder every driver makes. If you're lead footed, you will NOT see anywhere near the factory mpg. You must be light-footed as possible to obtain the best mpg. I used to drive the piss out of my car until I slowed down a bit and instantly got better mpg.
If you put your foot down farther, you're wanting more energy, which sends more fuel in. More fuel = more money. If you barely press your gas pedal down when taking off, I can still guarantee you'll get where you want to go, just a few minutes later. Instead of spending $1.50-$2.00 to get there, you may have only spent $0.75-$1.00. Please note I pulled that figure out of my rear end
#4: Follow Speed Limits
This mostly affects drivers on highways. "You can assume that each 5 mph you drive over 50 mph is like paying an additional $0.16 per gallon for gas" 
(https://www.fueleconomy.gov/feg/driveHabits.jsp)
With that being said, let's summarize for the individuals who may not be able to wrap their heads around this mumbo jumbo:
- Fuel system cleaner on occasion
- New tires are safer, but will lower mpg due to more rolling resistance.
- Drive more conservative, you'll still get there. I promise
- Every 5mph over 50mph is costing you an extra $0.16 per gallon. Slow it down, bucko!