Only if you have a specific reason for choosing another chapter, the original Guild Wars: Prophecies is probably the best choice for introducing yourself to Guild Wars. Nightfall may have more people playing in it now, but much of that crowd will move on to the next chapter when it is released. Prophecies has shown that it has staying power, as many old players keep returning to what they consider the Original Guild Wars game. This, combined with the smoother learning curve in Prophecies, make it prime for being the first Guild Wars you will play.

Easiest to pick up: Prophecies. The learning curve is much smoother than Factions, and the gameplay 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. 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. Prophecies has 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 avoids this. Factions also lends itself to solo play