The d20 would be gone. In its stead, you would use 3d6. Everything would follow the bell curve.
The removal of classes as straight-jackets. Classes are more like templates, skill-package-esque things than actual things you progress in. Your class determines what class features are available, but you purchase them with "job points," allowing you to pick which abilities you gain, and in what order. Changing class or picking new ones up is relatively easy, but balanced and useful.
Races are distinct from each other, with much mechanical space given to differentiating them. Picking a race has a life-long impact on the character and his abilities.
Social encounter mechanics exist, as complex and involved as combat mechanics. Combat rewards tactical thinking; social encounters reward roleplaying. AC would remain static, but the ability to parry, dodge, and block would enter the combat equation, which would be opposed rolls. Spells would require attack rolls, against rolled "saving throws" (in the 3.5 sense).
The in-game economy is fixed and made scalable, so that a setting can be silver-based or platinum-based, and either can make sense. The economy is driven by material costs, allowing the DM to manipulate these to give a different feel to each geographical area.
Item costs are based on material costs and skill of the maker, with the default assuming the crafter was average for the locale (we'll get to that in a minute) and "took 10."
Crafting is more involved. Rather than paying straight cash for raw materials, you must have the actual materials on hand. This is determined by what you are making, and if you are modifying it to have some specific property. Equipment is scalable, and pluses are not necessarily magical in nature.
Speaking of equipment, there is DR. Damage is based not upon weapon, but upon user, with the light, one-handed, or two-handed descriptor modifying that damage. All equipment has hit points, and suffers damage.
Cities have their own mechanics, as well; so does terrain. Cities have mechanics controlling availability of resources, general skill level of crafters, and most likely a few other things. Terrain mechanics allow the DM to determine what kind of materials can be found in a general area, the scarcity of those goods, the difficulty to get at them, and their base quality.
Also, skills and abilities decay if they go unused too long.
...I think that covers most of the main things that I would do, thus far.
