In normal mode, the buttons you have are: ABCDE

A,B,C are weak/mid/heavy attacks and normal specials
E is charge/launcher attacks and arcana specials
D is homing
Grab is a+d or a macro
Supers are A+B and the input
Arcana supers are stuff like 236236E and stuff

But in Simple mode...

A is normals. Mash a to autocombo A>B>C>Special>into super
there's a ground combo route and a launcher>homingcancel air followup route,
and some directions will do just a heavy and not an autocombo.

B is specials. Like Smash Bros, different directions get different specials.
Not every character has exactly 4 though, and there are no up-specials, as that just make you jump

C is arcana specials, which are directional, same as normal specials.

A+B is super. Characters with many supers cannot use all of them.

B+C is your Critical Heart (level 3) super.
If you can't use the super at that time, is uses an arcana move

A+C is Arcana Super. Again, you might not be able to use all of them.

A+B+C is still Extend Force. ABC again in EF is your 236ABC super.
ABC in the air does an Arcana super since you can't EFC in the air

You cannot use Burst in simple mode

E does absolutely nothing in Simple mode.

D is still homing, and as far as I can tell works exactly the same as normal mode
A+D or a macro set for that is still your normal grab
Actually, all macros seem to function exactly the same (though not all do the same thing as normal mode, obviously)

Superjumps and airdashes are exactly the same as well

So, what can't you do at all in simple mode? A lot of things
-optimal normal combos
-some special moves
-some arcana special moves
-Charged E moves, or E moves at all if they aren't in your autocombos
-214BC super
-Burst (This is an extreme drawback)
-Choose an arcana besides your character's default

What benefits does simple mode have:
-Easier execution of what you can do

If you're trying to take this game seriously as a competitive game, simple mode is not a good idea to use. However, if you're just trying to screw around, go right ahead and use it. Some characters have some benefits to the mode, like Kira, who gets to do 360 grab inputs with a single button, and some characters are hit especially hard by it.

Anyway, have fun playing the game.