I've stayed at several for work and I've been pretty happy with them all.
1. Residence Inn Marriott Downtown Bayfront. It shares the building with Springwood Suites. The Residence Inn rooms have a small kitchen. The rooms are "okay"--seemed like they were missing a piece of furniture or something (I had a King room and there was a big empty space with a small couch). But--they had one of THE best breakfast buffets in the morning. Pleasant staff, lots of variety, and the staff kept it cleaned up and refreshed. You will be very close to the Midway and all the bayfront goings on.
2. Embassy Suites Bayfront (not the older downtown one) - Again nice room, good breakfast.
3. Marriott Residence Inn Liberty Station - this is very near the airport and less walk friendly.
4. Marriot Marquis - A favorite with everyone, not always good deals on the rooms and right down in the waterfront area, very walkable.
5. Homewood Suites Downtown Bayfront - Very close to the cruise ship docks. You are down the hill from Little Italy so very walkable there but you have to go through a block of more industrial looking area. There can be homeless on the corner. Never bothered me but some people are unsettled. Free breakfast--so/so. Nice room.
6. The U.S. Grant - A Marriott hotel. It's in the downtown area which sounds good but it's not. Not much there but you can get to Little Italy or down to the bay/waterfront with a 20 minute walk. The deal with this room is the while the hotel has zero amenities like a free breakfast, the room itself is fairly luxurious with luxury shower products, etc. I would never choose to stay there but had to on a business trip. The bed was super comfortable.
5. The zoo is closer to all the hotels in Hotel Circle which is right off the 5. They tend to have better deals but you are right off the freeway and not walkable at all.
Those are probably all the places I've stayed. Just depends on if you're looking for a deal and if you have a desire to walk around at night after your daily sightseeing.