On the shelves of most hobby shops you’ll find fuels labelled “2-stroke” and “4-stroke”. Is there really a difference, or is this a big con by the fuel manufacturers to sell you more fuel?

The main difference is that most 4-stroke fuels contain less oil than 2-stroke fuels - typically 15% for 4-strokes and 20% for 2-strokes.

You’d think that because 4-stroke engines have more moving parts they would need more oil - not less. The number of moving parts has nothing to do with it. What is important is that, with very few exceptions, 4-stroke engines run substantially slower than comparable 2-strokes...most in the under 10,000 rpm range vs 13,000 and more for a typical 4-stroke of the same size. They are designed to deliver maximum power at slower rpm’s with bigger props.
The more slowly an engine turns, the less heat it generates from friction. If you don’t believe me, rub your hands together slowly, then as fast as you can.

So...lower rpm’s = less heat = less need for oil.
Four-stroke engines fire every alternate stroke, vs every stroke in a 2-stroke engine. Firing, or combustion burns fuel, which creates heat. Logically it may be deduced that if the engine fires every alternate stroke the engine has time to cool-off a little between combustion cycles.

Using, for example, a hypothetical 4-stroke engine turning 10,000 rpm = 5,000 combustion cycles a minute, vs. a hypothetical 2-stroker turning 13,000 rpm with 13,000 combustion cycles per minute, you can see that the 2-stroke has 160% more combustion cycles than the 4-stroke. Ergo: 4-strokes remain cooler, and therefore need less oil.
Because the 4-stroke is only firing every alternate stroke the glo-plug element cools down between strokes. Excess or unnecessary oil constantly dousing the element is going to make it more difficult to achieve a slow, smooth idle. If you’re one of those who say, "Too much oil can’t hurt anything”, you’re wrong.
In addition to causing undue friction in the engine, keeping parts from properly mating etc, too much oil in a 4-stroke fuel is constantly trying to cool a plug element that is already having problems. Like pouring a bucket of cold water on a bloke who is already shivering.

Since oil doesn’t (or shouldn’t) burn...it simply lubricates and goes straight out the exhaust all over everything...it does nothing to help us deliver power. However suppose we replace that 5% or whatever of unnecessary oil in the fuel with methanol which does burn. What do you know...greater top end power.
The conclusion to be drawn from all this is that a a properly blended 4-stroke fuel containing 15% oil will give better all-round performance than a regular 2-stroke oil containing 20% oil in the same engine.
While it’s not actually going to harm anything by running a 2-stroke fuel in a 4-stroke engine, don’t do it the other way around. It’s not going to have enough oil.

The manufacturers of YS engines - the most powerful 4-stroke engines available - recommend their engines be run on fuel containing 20% oil. These engines are quite unique in many ways and the manufacturer’s recommendations should be followed.