Easiest to pick up: Guild Wars Gold. The learning curve is much smoother than Factions, and the game play less complex in its entirety, while Nightfall gets rather complex towards the end of the storyline about Guild Wars Gold.
PvE enjoyment: Prophecies and Nightfall. While these two are neck-and-neck among the GuildWarsGuru.com community, Factions is generally agreed to be an inferior game to the other two about Guild Wars Gold. While each chapter has its fans, there are many more fans in favor of Prophecies and Nightfall than there are Factions.
Group play: Nightfall. The largest population of players tends to be in the newest chapter, as old players move on to new content, while new players who have just bought the new chapter have nowhere else to go to get Guild Wars Gold. Prophecies have seen less of a decline than Factions in terms of people playing in those chapters missions, but both have less players than Nightfall does. Of course, when chapter four is released, there will no doubt be a mass migration to that setting, leaving the Nightfall lands less crowded than they are now about Guild Wars Gold.
Solo play: Prophecies or Factions. While Nightfalls Heroes make a strong argument in favor of Nightfall being the chapter best suited to the player who would rather avoid grouping with other human players, Nightfall becomes rather difficult near the end of the storyline and drives many players to grouping with others. Prophecies largely avoid this. Factions also lend itself to solo play
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