Diablo

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.