Hard to choose any single one...

1. Inventory (Management)
Rather than taking up informational space in remembering the precise location of items within the inventory grid, all is automatically sorted and the bag dividers have been replaced with customizeable filters. The inventory grid itself can now be made to be continuously scrollable (in either direction, vertical or horizontal) and the background can be faded out at either end. You can also specify shortcuts to jump to a customizable inventory type (e.g., just gear, or just equippable gear, materials, just materials usable by your current crafter for recipies that would grant experience or, if capped, be usable only at level cap, etc.), and can customize sort orders broadly or per inventory search type.
2. Classes
Unless we're actually going to make use of them, cap classes at level 30 (i.e., 1 xp from level 31), further forcing them to be upgraded to jobs. Remove soulstones. Once the class has upgraded to the job, there's no going back; the job replaces the class. This should save us some data.
3. Armory Chest
Removed. Those spaces move back into the broader inventory.

Clicking on a given slot will immediately show all other items (within customizably filtered results) that you can equip instead, in sorted order, and you may set weights for your Optimize button, allowing Optimize to favor certain sub-stats over others, etc., before and after set resultant parameters of a given stat (10% greater MP generation, 10% GCD interval reduction, etc.).
4. Job Selection
You may now select jobs directly instead of specifying a gear set. It will automatically apply the Optimized set for that job (per the last optimization profile used on said job).
5. Glamour
Now attached to slots, not gear, and varied by job. Unlock the appearance, account-wide, of any item you spiritbind.
6. Secondary and Tertiary Stats
Spell Speed and Skill Speed have been consolidated into Speed. Critical Hit now affects only Critical Hit chance, not value, with crits again being standardized at +50% unless guaranteed; effects which "guarantee" and effect count as if increasing that chance by 100% and excess chance is instead converted into proportionate bonus effect (120% chance of a crit for 50% bonus effect becomes a 100% chance of a crit for a 60% bonus effect).

Tenacity, Piety, and Direct Hit have been moved to a new class of stats, called Tertiary Attributes, and have been revised.

Tenacity no longer increases damage dealt, but does increase the %HP damage necessary to be knocked back or debuffed by attacks whose effects may be nullified by dealing 0 damage. Piety has been replaced by Vigor, which also increases %HP generated per tick. Direct Hit has been replaced by Mobility, which increases your passive movement speed and the effect and duration of your movement speed buffs.

All left-side DoW/DoM gear includes one Tertiary stat in addition to its major and minor secondary stat.
6. Materia
Materia no longer exists as items, and the Spiritbond meter has been removed. All existing materia and Spiritbond will be converted into Essence (Ruby, Emerald, or Azure). Extract Materia, too, has been removed. Instead, you automatically gain tiny amounts of Essence from any activity that would increase your Spiritbond, simply removing the chore between generating and actually acquiring Materia. The type of Essence that a piece of gear will generate is based on its dominant secondary stat.

Gear no longer slots materia. Instead, you add Materia directly to your jobs, up to a maximum determined by the maximum ilvl that job may equip. "Ornate" gear now instead boosts the effect of your Materia by 5% and accounts for this in its Optimize weighting. Crimson, Golden, and Violet Essence turn into different secondary stats dependent on the type of class/job to which it is added.

On a Disciple of the Hand, Ruby grants Craftsmanship, Emerald grants CP, and Azure grants Control.
On a Disciple of the Land, Ruby grants Gathering, Emerald grants GP, and Azure grants Perception.
On a Disciple of Magic/War, Ruby grants Determination, Emerald grants Speed, and Azure grants Critical Hit for secondary stats, and for tertiary stats Ruby grants Tenacity, Emerald grants Mobility, and Azure grants Vigor.

Tertiary and Secondary attributes use separate caps, though Tertiary attributes may exceed their own at cost to Secondary attributes; Secondary attributes cannot exceed their own by borrowing from Tertiary. (You can sacrifice output stats [Secondary] for QoL/cheese stats [Tertiary] but cannot sacrifice QoL/cheese stats to gain further output.)