If you don't want to read through the huge list of changes here is the cliff notes version.
1.) Reworked material system. Materials and weapon effectiveness is now based on material properties and not a flat modifier.
2.) Completely reworked wounds system. Hitting someone with a sword adds a cut (or worse) to the person instead of subtracting hitpoints from an abstract body part.
3.) Completely reworked health care system. New doctors and surgeries. Just like medivial era people are likely to die from bleeding or infection.
4.) Completely reworked military. Training now included watching instruction and personal drills. Squad controls completely different. Uniforms are much more customizable. Dwarves won't just grab a random sword, they grab one based on what you tell them. Could just be a specific material sword or a specific item.
5.) New underground features. Every embark is pretty much guaranteed underground caves, magma and HFS. Old bottomless pits, chasms, and such are gone.
6.) New megabeasts. Random ones both above and underground varieties. Old ones are still around. Megabeasts are also a lot tougher.
7.) HFS and clowns are all different. The old one per region tile clown car is different. Have fun.
8.) And most important. Underground farms must be on mud! Underground soil is no longer sufficent.
There are other minor changes like dwarf personalities and how nobles are selected, but it isn't too major.