Pepto, it depends on what you're into. The style of story/setting you enjoy. Prophesies, the first campaign, is styled more like your typical D&D "slay the dragon and rescue the world from the evil might" plot. It's quite medieval, IMO. It's also extremely slow-going and takes quite a long time to level up your character. It's balanced somewhat by your ability to earn skills for free by completing quests. No other campaign offers that, which is kind of a shame. :P It uses the six core classes: Warrior, Ranger, Monk, Mesmer, Necromancer, and Elementalist.
Factions is more, well... Asian. :P You'll find yourself in more exotic, mystical places, from a holy school of warfare to a sea of jade. Also a blighted, crowded ghetto city with narrow streets and deadly gangs. The plot's a bit linear, but it doesn't fail to entertain as long as you turn down the speakers before Vizu or Danika say a line.

Besides the six core classes, it also introduces two new classes -- the often-abused Assassin and the spirit-calling Ritualist.
Nightfall has more of an Egyptian/North African theme to it. The plot in this one runs a bit deeper; I won't spoil it for you but you're not just after some random power-hungry wizard or warrior this time. It's still somewhat linear, but you're still offered a few more branches of storylines to explore. Nightfall also allows you to use heroes, which are customizable NPCs you can equip and take along with you. Extremely useful.

The two new classes (plus the original six) are the partywide supporter Paragons and the magical melee Dervishes.
Eye of the North is an expansion; you need one of the first three to play it. It adds to the lore and gives closure on certain events in Prophesies, but it doesn't introduce new classes and it's not very long compared to the others. I'd advise playing through a little bit before deciding if you want more.