Amy & Brandie,
I think San Francisco is one of the most progessive and open cities around. I hold hands with my partner almost everywhere in the city and I see a lot of women couples doing the same. I think you'll find complete freedom to be who you are here.
I think the harder transition for you two will be from small town to bigger town. The bigger more populous neighborhoods: Castro, Downtown, Pacific Heights, the busy part of the Mission - all are fine and safe. Violence against gay/lesbians for who there are is nearly unheard of here.
That being said, it is a city and there are time where you'll have to be more vigilant and on the watch for more standard crime (theft, harassment, etc). There are neighborhoods that are best avoided and even in good neighborhoods you should be more alert at night if there aren't a lot of people around.
Overall, I feel *very* safe in this city and I think you will do too.