One word (well acronym really): EPA.
Cut from Fallout 2, it would fit in perfectly in the Mojave, placate people that felt too much of the "goofy" flavour of FO1-3 was lost in New Vegas without forcing people to include it and finally include one of the most epic locations ever into the Falloutverse.
Failing that, I'd love a bus from Vegas to Reno. You could include plenty of real-world reference into it (real-life buses, mostly for old people, do exist that go from LV to reno. Give the bus driver a red hat for added humor factor, like those seniors "red hat society" sponsored gambling junket buses). The only trouble would be deciding which of the FO2 endings for Reno was canon. I vote for the Chosen One's bastard daughter taking over reno under the auspex of the Bishop family, it would tie into the reference to the Bishops already in FONV, we know canonically they're still a major player in Reno.
Oh, and tying in to the "song names are quest names" theme in FO:NV, you could title a quest "folsom prison blues" and have the player shoot a man in Reno just to watch him die.
Ah, EPA would be so kickass.
Played it on the Restoration Patch, the Spore Plants were annoying as hell, and dogmeat and marcus went ape[censored] on 'em.
Had to sit down and read a book and every once in a while hit the space button.

But the rest of the place would just be awesome.
The puzzles should not be easy though.
Should be really hard and complicated which makes the struggle all that more worth it.