I'm right-handed, and I normally hold the N900 with my left and operate it with my right. Somehow I feel rotating the N900 (from horizontal to portrait) anti-clockwise would be better? (meaning, the speaker piece should be on the right side when phone is horizontal).

Does anyone know the (technical) benefits N900 was designed with this orientation?

In the car, I normally leave the phone next to me (I'm in a country with left-hand traffic) so my phone will be on my left. I always pick it up in reverse and need 1 extra step rotating it - I guess these phones are designed for right-hand traffic?

Seconded. I've been using an N900 for a year, and it still feels backwards.