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******* WARNING: POSSIBLE MAJOR SPOILER ALERT! *******
(Don't know if this is really all that bad of a spoiler or not, but just incase)
Naming major milestones will probably be somewhat a matter of oppinion. But if I were to break it down into what
I consider milestones, it would look something like this:
1) Searing. Graduating from the noob area.
2) Yak's Bend. Out of the old, ugly Ascalon area and into the snowy mountains (Northern Shiverpeaks)
3) Lion's Arch. Thawing out and finally getting to some green lands again.
4) Hard to pinpoint a milestone here. You teeter between lush green and more waste land for a while. Ventari's Refuge is probably as good a milestone point as any, mainly just to break up the long stretch between Lion's arch and...
5) Crystal Desert. Here's where you start getting your first taste of real challenge.
6) Ascending and reaching Droknar's forge in the Southern Shiverpeaks. Now everyone is 20 (except the brave/insane few that traveled south from Beacon's Pearch prematurely) and you can get your best (stat-wise) armor. Playtime is over at this point.
7) Reaching Ember Light camp in the fiery islands area. It's hot, it's ugly, it's hard. Good fun.
8) Beating Hell's Precipice. That's it for missions.
9) Fissure of Woe and Underworld in Temple of Ages. (unless you're in Europe

) Technically, you COULD do this much sooner, but I'd personally recommend doing all the missions first to get as familiar/comfortable/skilled with your character as possible, because these places do NOT mess around. You go in with a good, solid, well-rounded group that can cooperate or you spend 1000g on a 15 second beat down (includes travel time).
After that just PvP to your heart's content.
