There are lots to see in Hokkaido! It also depends on which season you are planning to visit. If it's winter, it is very hard to travel around Hokkaido because you will have to drive in snow and some roads may close in winter.
Here are recommendations from my experience.
Hike in Shiretoko (especially the Goko Lakes), Visit lakes like Lake Toya, Lake Akan, Lake Mashu, Lake Shikotsu, etc they are beautiful, summer activities in Niseko such as canoeing, enjoy fresh vegetables especially corns, beer garden in Sapporo, lavender field in Furano, etc.
Skiing in Niseko or other ski mountains such as Sapporo Kokusai, Kiroro Ski Resort, etc., the quality of snow in Hokkaido is amazing.
Winter hot pot dishes like Ishikari Nabe and some winter seafood such as Shirako.
Snowy sceneries in Biei, frozen blue river, snow hike, winter canoeing in Kussharo River, Stay at the Ice Hotel in Tomamu, etc.
Indulge in great seafood dishes - in my personal opinion, eastern Hokkaido such as Kushiro has more delicious seafood than cities like Sapporo. (I have never been to Hakodate though, they might have great seafood, too)
Visit to Yoichi Whiskey Distillery - nice place to take a walk even if you don't enjoy whiskey. If you do enjoy whiskey especially Japanese or Scotch whiskey, here is a must-visit!