Next month my twins start freshman year at a massive (4,000+) high school. Nervous? Probably me more than them. Something that helps, based on my older son's experience, is the school's student advisory program, which pairs each group of 25 or so teens with a teacher who can guide them through the transition to high school. They meet every day with that teacher, but the secret weapon is an upperclassman -- a "senior helper" -- who comes in regularly to answer the newbies' questions based on personal knowledge of the school's challenges and opportunities.
Another way to go is linking each freshman or new-to-the-district student with a peer mentor who can show them the ropes. DoSomething has some nice tips for taking this on as a leadership program.