Factions: The factions in Skyrim are independent from the Vvardenfell factions. For example, even if you're the boss of the Vvardenfell Fighters Guild, you'll still have to begin anew in the Skyrim Fighters Guild. To get started, you can find the Skyrim Mages Guild and Skyrim Fighters Guild halls in Karthwasten. The Skyrim Thieves Guild can also be found in Karthwasten, in The Droopy Mare Inn.
Wilderness: The wilderness in Skyrim can be tough for new players; most creatures are hostile. Skyrim is home to creatures like spriggans and bears but also houses a lot of bandits and outlaws.
Diseases: Skyrim adds no new diseases.
Items: As you travel through Skyrim, you will discover that the mod has added a huge amount of items to the game, from new Books to dangerous weapons.