Not counting any ports, I'm going to say Super Smash Bros. Brawl. It's fun by yourself, and especially fun with friends. It has a lot of options to tweak your VS game, a fun 1P experience and target tests which can be addicting. There's also tons of trophies, songs and stickers to collect for fun. And don't don't forget online play. Basically, it can keep you entertained for a looong time, and is a must have if you own a Wii.
Ports that are really good include Resident Evil 4, Twilight Princess and Okami.