Consider an Amtrak USA Rail Pass and head from S.F. to Los Angeles > Las Vegas > Chicago > Washington D.C > New York > Boston
http://tickets.amtrak.com/itd/amtrak/selectpass
The Western US is all about the scenery and National Parks. The Greyhound bus will not take you there. It will drop you in the inner city and you'll need a car. Route 66 doesn't really exist any more. The remaining parts are overrated and pretty boring. If you drive a car here is a suggested itinerary.
From San Francisco go to Yosemite National Park
http://www.nps.gov/yose/index.htm
Drive through the park across Route 120 and Tioga Pass, the highest vehicle pass in CA, climb thousands of feet on a mountain road and reach the Alpine meadows of Yosemite.
From there head to Lee Vining and Mono Lake.
The lake is in a caldera of an extinct volcano.
http://maps.google.com/maps?f=q&source=s_q&hl=en&geocode=&q=mono+lake&sll=37.88786,-119.281311&sspn=1.604034,1.790771&gl=us&ie=UTF8&ll=37.956109,-119.215393&spn=0.774205,0.895386&z=10
From there take U.S. Route 395 south to I-15 and head to east to Las Vegas.
Route 395 runs along a fault line along the Sierras and you'll get a view of Mt. Whitney. The geology is pretty wierd. You pass through the Owns Valley. It is is a graben; a downdropped block of land between two vertical faults. The rock formations are really stange.
Spend some time in Vegas and get up at dawn and head north to the canyon country of Southern Utah.
Do the "Great Circle Tour" to see Zion, Bryce Canyon, Capitol Reef, Arches National Parks and the Grand Canyon. Bryce is one of the most fantastic sights in the southwestern U.S.
http://www.nps.gov/brca/
http://www.nps.gov/zion/index.htm
At Bryce Canyon everyone stays at Ruby's Inn.
http://www.rubysinn.com/
You can cross the Colorado River at Lake Powell
http://maps.google.com/maps?sourceid=navclient&rlz=1T4HPIA_enUS314US314&q=lake+powell+az&um=1&ie=UTF-8&split=0&gl=us&ei=SPibSvXTHZKyswOMn9yUDg&sa=X&oi=geocode_result&ct=image&resnum=1
Utah Route 12 is one of the most scenic roads in the country. Red Canyon and Big Thunder Road in Dixie National Forest is the inspiration for Disneyland's Big Thunder Mountain (see the picture I took in link below)
http://en.wikipedia.org/wiki/File:RedRockUtah.jpg
http://www.utah.com/byways/highway_12.htm
http://scenicbyway12.com/
Also check out the Hoover Dam tour, It's right outside Las Vegas.
http://www.usbr.gov/lc/hooverdam/service/DamTour.html
Head to Phoenix or back to Las Vegas and take a plane to Chicago.
Chicago is one of the cultural centers of the country. There are tons of things to do there.
Art Institute of Chicago
Adler Planetarium
Shedd Aquarium
Field Museum
Museum of Science and Industry
Architecture river boat tour
The new glass bottom Sears Tower viewing platform
Navy Pier
Major League Baseball
Shopping along Michigan Ave.
Great restaurants (Harry Caray's)
Theater
Shows
BTW The Art Institute has one of the largest collections of Impressionism in North America as well as an incredible medieval armor collection. Don't miss it.
http://www.artic.edu/aic/collections/eurptg
The Architecture river boat tour is a great way to see the city and learn about it's history. You get a spectacular view of dozens of skyscrapers and other important buildings. It's a relaxing 90 minute tour on the river in the heart of the city.
http://www.cruisechicago.com/tours.php
Here are some other links to attractions.
http://www.chicagotraveler.com/chicagos-largest-attractions.htm
http://www.chicagobreakingnews.com/2009/05/a-glass-bottom-skydeck-for-sears-tower.html
From Chicago head to Washington, New York and Boston.
Walk the Freedom Trail in Boston. It takes you everywhere you want to go, including the North End, which has the best Italian food in the world. The gelato is to die for. Other stops include Paul Revere's house, the Old North Church, Faneuil Hall, Old Ironsides (U.S.S. Constitution), and Bunker Hill. The tour of U.S.S. Constitution is really neat. Faneuil Hall is where everyone goes to meet, shop, and hang out. (Lots of street theater and other interesting things.)
http://www.faneuilhallmarketplace.com/
http://www.aviewoncities.com/boston/freedomtrail.htm
The Museum of Fine Arts has a great collection
http://www.mfa.org/
There is a real interesting museum at Harvard. They have a botanical collection reproduced in blown glass. It's pretty amazing. Take a walk around the campus and Harvard Square.
http://www.hmnh.harvard.edu/on_exhibit/the_glass_flowers.html
For seafood go to one of the many Legal Seafood locations.
http://shop.legalseafoods.com/?source=google&page=homepage/pd/1
Boston cream pie and Parker House rolls were created at The Parker House Hotel. Stop by for dinner. BTW you can order dinners rolls to go and they sell slices of the pie in the gift shop.
http://www.omnihotels.com/FindAHotel/BostonParkerHouse.aspx
BTW if you plan to go to more than one National Park, buy the annual pass. It allows a car an it's occupants into any National Park. it's cheaper then paying regular admission and it's good for a year.
http://www.nps.gov/fees_passes.htm