Macworld San Francisco is the best to attend. At the heart of Silicon Valley, San Francisco is a great location and is already home to thousands of Mac users. If it is your first time, you arrive with no idea where to go and chances are you are thousands of miles from home with forty thousand other Mac users. If you ask for directions, they probably are there for the first time too, and are lost as well. Just so you look like you know what you are doing, and have a clue I suggest reading the following.
If you plan on seeing the city, I would recommend arriving one day early. If you do not plan on attending Monday sessions, then get there on Monday morning, check in and explore the city that afternoon. Schedule a 12-3 AM flight so you can sleep on the plane and arrive at 8-9AM in San Francisco. From there, you will get downtown by 11AM due to baggage claim and waiting for the super shuttle. Dont get a taxi unless you have thirty dollars to blow. Super Shuttle is 10 dollars I believe and takes longer than a taxi because they are dropping off a dozen other people in town but you will save a lot if you are going to and from the airport. You can schedule a pickup from your hotel on Super Shuttle at (http://www.supershuttle.com/htm/cities/sfo.htm).
Taxis are 4.50 to go eight blocks. Not bad and it beats a 40 minute walk twice a day. The closer you get to union square, the more expensive the hotels. I was four blocks from union square one year and paid $129 a night. You can pay about $100-$299 a night depending on how you plane. Price line is a great resource for great rates and if you belong to an online community, some are offering special rates for their members. Your Mac Life is one of the more popular groups to do events during MacWorld for their listeners. Anything more than 10 blocks from the conference center will become trouble and make the commute not worth it at all.
Do not eat the lunch at Mosone center. It is overpriced and crap; reminds me of lunchroom food in high school. There is a brewery with great sandwiches across the street from Moscone on the east side with a Starbucks coffee beside it (for those that get up at 2 AM for the keynote). Across the street, north, lies the Sony Metreon. The Metreon has 24 high-class theatres, four restraints, a Sony store and arcade. You can get lunch from the place and take it to the courtyard or garden that is on the third floor. The Metreon is beautiful and is extremely close. You can also walk a block North for some small shops and fast food like McDonalds and Jack in The Box.
Dont wander around the city without having a plan. San Francisco is beautiful and the Conference is awesome but get a booklet (sent to reregistered attendees) with the list of conferences and hours of operation. Find out what you are allowed to attend and make your schedule so you can attend those. Other times spend time on the floor playing with products and getting free stuff. Unless you are attending a late conference, leave by 4PM and just walk. Get on the subway and explore golden gate park, fishermans wharf, and Castro district. I would also recommend renting a car for the evening, get a map and drive around the city. It is awesome to go to the residential area about five miles outside of the city. There is a large mountain and you can go to the top and see everything (great for photo ops).
If you belong to an online Mac community or User group, find people that are attending and have dinners or walks. You are less likely to get loss if you go with 3 or more friends. There is nothing wrong with exploring but be sure to bring a slow person so if you get jumped, you can trip them and run. When you get home, block them from your AIM list and hope they dont try to contact you to pay their medical bills for a stab wound. Never happened to me, I swear!
That sums it up for those that have never been to San Francisco before and will help you get around. Always plan with plenty of time. Even if you arrive early, better than being late. That counts Airline, hotel, dinner reservations, car rental, conference sessions and especially the keynote. Arrive at 2AM-5PM to get a seat where you can at least see Steve without having to look at the Jumbo-tron. Last year, the first two in line arrived at 1:30AM. Just arrive, and then put on your iPod and chill. This is why I recommend getting there a day early. Get your badges; find Moscone, tour the city and go to sleep at 5PM so you have plenty of rest for the next day.