Biggest change, imo, is the addition of Terror Zones. How this works is that a number of zones in each act can become terrorized (one at a time, lasts for 1 hour, changes to a different zone after that). When a zone becomes terrorized, the monsters there will adjust to your lvl+2 (champions and bosses adjust +4 / +5), with all consequences of that, e.g. they grant the respective xp and their treasure class also changes accordingly (which means they can drop better loot). Terror Zones open up after killing Baal in that difficulty, so you'd need to beat the game before you can start farming terror zones. However, these zones (in hell difficulty) are really one of the prime farming spots now and also help to level once you're in the 90's as you're not bound to xp penalties due to outlevelling monsters.

Second biggest change is the introduction of Sunder Charms (only obtainable in hell terror zones) which allow to break immunities (each immunity has their own charm). This makes it really viable to go for single element builds now.

BEside that there are a bunch of new runewords and fixes to skills (ias calculation has been changed on some skilles and next hit delay has been fixed among other things), which opened up quite a few new builds.

Mostly bug fixes honestly. Some skill viability as well, like Fist of Heavens. Some new runewords as well. You can also kill the Cow King and still open new portals to the Cow level. Enough to keep it fresh but not too much to get overwhelmed. You could prob even read through the patch notes and get to grips with it all.

Can't cheese a3 anymore, people constantly getting confused when it doesn't work.

Now at least one person needs the organs and break the orb, but it counts for all present in game