Imagine you want to help blind people.  You're considering two charities: one that trains seeing eye dogs, another that performs cataract surgeries. You check Charity Navigator and find that they have roughly similar overhead expenses, and neither looks like a scam, so does it matter which one you pick? It turns out it matters a lot. By the charities' numbers, a guide dog is very expensive (~$50,000) while cataract surgery is much cheaper (~$25).  Assuming you think curing blindness in one eye is about as good as providing a seeing eye dog and training someone to use it, a donation of $200,000 to a seeing eye dog foundation is equivalent to donating $100 to a third world cataract charity: each helps four people.
I'm using charity-provided figures here but really we want independent evaluation. It's so easy to fudge things when you're just giving a single number and not being transparent about what went into it. These are also average-case numbers, or even best-case numbers, while the number we actually care about is the marginal cost: what will my money let them do they couldn't do otherwise? I suspect that if you got good marginal cost data the difference in cost-effectiveness between "seeing eye dog in the USA" and "cataract surgeries in the third world" would be closer to 100x. ($100 to surgeries is then equivalent to $10,000 to dog training.)
Even still, that's a very large variance in efficacy. It's high enough that researching the impact of charities, or making sure you're using the best research that's already out there , goes farther than cutting expenses to have more to give or even trying to make a lot of money.
 In general it doesn't make sense to pick a cause first. We should instead be open to excellent giving opportunities in any field, judging them all by what we get for our money, but it simplifies this post to limit ourselves to easily comparable charities.
 Some searching brings up these examples from charity websites:
Guide Dogs of America:Q: What is the cost of providing a guide dog?Guide Dog Foundation For the Blind:
A: Approximately $42,000 or more, which includes the cost of training the dog and providing instruction for the guide dog user.Q: How much does it cost to train a guide dog?Fidelco Guide Dog Foundation:
A: It costs more than $50,000 to complete the training of one guide dog. This includes all expenses from breeding to raising the dog to training it and matching it with a blind person.Each guide dog costs Fidelco approximately $45,000 to breed, train, place and maintain for its average 10-year service life. Fidelco provides guide dogs to its clients at no cost.Himalayan Cataract Project:For a cost of about $20, these patients get approximately the same surgery that was state of the art in America 10 years ago.Fred Hollows FoundationIn some countries, sight can be restored for as little as $25.
 Which, as far as I can tell, is GiveWell's.