Flying from San Francisco to Las Vegas or other points east is tricky; between mountains and restricted airspace there are very few ways to go. The usual VFR route is something like KSQL KWJF KDAG KLAS, 436nm at 9500'+. That carries you out of the mountains near Palmdale and south of all the restricted space in California and Nevada. It gets boring; I recently learned of another route via a desert town, through the Trona Gap.
The route is roughly KSQL L05 ODGEE SERUE L72 KLAS, a series of wiggles through a narrow corridor between R-2505 and R-2524. That's 390nm, saving 46nm or about 10% of the trip. The mountains are awfully high west of L05, I'd want at least 10,500' crossing there or else go south towards Bakersfield first to come up the river valley (adds 20nm). Either way it's more time over rough terrain than the Palmdale route, but at least it's something different.
I'd only try threading this needle with flight following and a trustworthy GPS. R-2505 and R-2524 are active at all altitudes all the time. R-2506 is only Surface to 6000' during the daytime so you can shave a few miles off the route above. Apparently it's not uncommon to be cleared to enter R-2505 above 10,000' which could save some 17nm. On the other hand the Edwards AFB info says they sometimes close the Trona gap entirely via NOTAM. Plan accordingly.
Another alternate route I've flown in the area is via Yosemite, the Tioga Pass, and the Owens Valley. Something like KSQL E45 O24 KBIH O26 L06 KLAS (394nm). It's a fascinating trip through a part of California I'd never seen before and KBIH is a nice stop for fuel and excellent Thai food. Not the simplest route: the Sierra crossing is tricky and wind is a concern both in the mountains and in the valley.
Disclaimer: I've not flown most of these routes and have not confirmed altitudes, airspace, etc. The terrain and weather in this area can easily be dangerous. Don't take my word for these route ideas; you're responsible for your own flight planning.
Thanks to Kareem Fahmi from California Airways in Hayward for pointing out the Trona route. Kareem also wrote up a great little pilot's guide to California airports.