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Lake Tahoe resident here!  Which part of the lake are you going to (north, south, west, or east)?  It looks like you're coming in October, which is definitely cooler than summer time, but perfect in terms of less tourists.  Let me know where you'll be and I'll give you some suggestions.  :)

Zephyr Cove is not very far from Stateline (the border between CA and NV).  I would guess it's only 5 or 10 minutes.  And you're in a great place!  You'very close to everything!

If you are looking for scenic drives, try taking the Hwy 50 loop.  It goes all the way around the lake and the views are incredible!  Also, nice places just for getting out and walking nearby include Sand Harbor (maybe 15-20 minutes north of where you are) and the Heavenly Village at Stateline.  You just drive south toward CA and there's this big complex or stores, restaurants, etc... right next to the casinos.  Of sourse, you will be near the casinos, so if you're into gambling I would recommend either Bill's (it's smoke free) or Harrah's.  There are always shows going on at the casinos, too, so you might want to check out their websites for comedians, singers/bands, and other performances happening during your stay.

One of the coolest things I love to do with people who come to visit is take one of the (many) boat tours offered up here.  The Tahoe Queen (http://www.boattahoe.com/tahoe-queen-dixie-cruises.htm) is this awesome big paddle-wheel boat that takes you on a tour around the lake.  On the same site is an advertisement for the MS Dixie, which does really great dinner cruises.  Also, during October is the Kokanee Salmon Festival!  Basically, all of these red salmon swim upstream to mate.  It's incredible to see the whole river red with fish.  Here's the website http://www.fs.fed.us/r5/ltbmu/recreation/visitor-center/events/kokanee.shtml. While you're here, you probably want to enjoy the outdoors.  Lots of places rent bikes, and there are tons of biking or hiking trails around.  You'll also be really close to Squaw Valley, which is where the Olympics were held in the 70's.  Kinda cool. 

For cheap, awesome food, I love Freshie's in South Lake Tahoe.  It's a locals favorite.  Also, there's the Mandarin Garden for Chinese and Orchid's for Tahi (seriously, the best Thai I've ever had!).  If you want some really romantic (and higher priced) restaurants, I recommend Ciara's Steakhouse or the Chart House.  Here's some restaurants to stay away from because they are all overpriced: Womack's BBQ, The Riva Grill, and the Harrah's buffet.  You can get much better food at much better prices than at these place, imo.

I'm not so sure about driving to San Fransisco and staying the night there for several reasons.  1)  It's going to take you almost 4 hours just to get from Zephyr Cove to the Bay are.  And more to find your hotel in an unfamiliar town.  2)  It will take you so long to get there that you probably won't have much time to really enjoy San Fransisco.  My opinion is that if you have never been there you probably want to do all the cool touristy things, which you wouldn't have much time for.  3)  The San Fransisco airport is BIG and takes time to manuever around in. 

If you want to see the big city, I would recommend going to Sacramento instead.  It's relatively large, only 2 hours away, and has a much more manageable airport.  Plus Old Sacramento is super cool!

 Wow, this is super long.  If you need more info, let me know.  I'd love to help!

Yeah, Yosemite is like 4 hours away.  Even if you left early in the morning, it would be hard to take in much before you'd have to leave for the night.  We've taken a couple day trips to go down there for biking or hiking, but we usually leave at about 4 am in order to be there early enough to enoy a whole day.

The Loop around the Lake takes a few hours.  You could definitely do it one morning, or one afternoon, so maybe a half-day event.  It's really beautiful (one of the most scenic drives in America), and there are lots of cute little towns/shops/restaurants along the way.

I also think the drive to Sacramento in great, though.  Right as you're leaving the basin you go over this pass that is just incredible (maybe less so if you're not into heights :).  I think Sacramento is definitely doable, and almost as close as Reno.  It takes us about an hour and a half to get to Reno airport and about 2 and a half hours to get to the Sacramento airport.  Sacramento is also much more interesting of a town than Reno, imo.  Maybe I'm a little biased.  :)