If your players want a tough game?
Reign of Winter. And use the environmental rules constantly. Further, rule that the presence of Winter Portals are causing all of Golarion to have wintery weather by the time Book 3 comes about, so any and all fights outdoors are set during snowstorms. If you want to be even more evil, have a Winter Portal exist in the alien world that is Book 4. (Don't bother with winter weather in Book 5. Having it NOT be present will cause the players to go buggy. Having tech used against them (but don't describe it as tech, describe it as alien magic or the like) will have them freak out. ^^
That said, if you only have a couple experienced players? Go with Runelords. Classic game that is quite enjoyable. Double the encounters and sizes of rooms because of the double-sized group.
I suggested that but, they wanted this one more so I'll make it work.I will do what I can to make the game work well w/o mythic rules then.
I will just have to pay attention to what changes need to be made for the later books.