- Brand new universe and lore - including the characters, cities, factions, 300 year history, etc.

- Brand new central game mechanics - ship building, crew hiring, & more

- Collision of and improvement of mechanics from earlier games previously separate - settlements of F4, skill trees & perks are a combination of Skyrim and F4, some inspiration from NMS as seen in the ore mining and fauna scanning, not to mention spaceflight & dogfights (although not unique to NMS), etc., all mushed together in one game

- Engine overhaul and many technical improvements

- Experimental use of proc-gen - to my knowledge, it hasn't been used in this way at this scale: ~1000 massive planets, generated beforehand and then touched up, in a single-player RPG

It's a new game, even in the strictest standards.