The amount of player traffic a site gets can be very important.  At the end of the day biggest is often the best in the online poker world, because more action means more money and more game choice.  With that in mind here are the biggest poker sites/networks for European and American players.

4 biggest poker sites for European Players

PokerStars
Full Tilt
Party Poker
iPoker Network (eg Titan Poker)

4 biggest poker sites for American Players

Pokerstars
Full Tilt
Cereus Network (eg Ultimate Poker)
Cake Network (eg Cake Poker and Doyles Room)