It depends on how much heat you can take if you can make it in mid-summer. Usually the humidity is very low, and that allows the temps to drop to comfortable levels at night.
What route are you taking across the Sierra? I would not recommend 50 from Placerville to Tahoe. The only time I drove it, it had heavy traffic and no shoulders. The next pass south is much better, along the Mormon Emigrant Trail Rd and/or US 88 (Warning: the MET has no water, streams, or services along its 35-mile climb from 3000 to 8000 feet, maybe 88 would be a better uphill choice.
Taking the Donner Pass route (i-80) has lots of campgrounds and services along the way, but you need a clearly marked map, there's a lot of turns on surface/frontage roads with "bonus" extra steep climbs in the lower elevations, and you ride on the freeway shoulder for some sections. North of Donner, taking 49 over Yuba Pass has some winding climbs and descents, but rivers, campgrounds, and quaint small Gold Rush towns to get supplies, then one can take 89 south to Tahoe and 50.
My real favorite pass would be Hwy 4, south of 88. There's two state parks with hike and bike sites along the route to Tahoe, Calaveras Big Trees and Grover Hot Springs, and the scenery is fantastic. There are streams and lakes along the route once the road gets off the big ridgetop it follows all the way up from the Gold country, once past Bear Valley, and some general stores along the route. Be warned that this has the most difficult climbs and winding descents of all the passes I've listed, and there's a maybe 30 mile stretch between Lake Alpine and Silver Creek campground with no piped water or any services--but with the most spectacular scenery, though.
Last edited by stevepusser; 08-05-12 at 06:47 PM.