One of my favorite charities is
http://www.modestneeds.org.
They provide help to meet life’s little emergencies for people with low incomes. It helps people avoid spiraling into poverty or homelessness by providing small grants to people who would otherwise fall through the cracks. An unexpected car repair, high heat bill and similar things often push low income families to the edge. This organization helps meet those needs and is one that I support.

I agree with Amy that modestneeds.org is a quality charity and one that I give to on a monthly basis.

If there is a major disaster in the world, I tend to donate to DoctorsWithoutBorders.org

While not specifically a charity since you don’t get a tax write off for donations, I am also giving out more micro-loans through Kiva.org

I believe all are worth checking out to see if they might be something that you find worthwhile to support.

There are so many important causes it can be very difficult to choose. I try to tell myself that so long as everyone picks something important to them, many things will get covered. I cannot do everything myself!

Many people are motivated to give to local charities and to fight causes that hit close to home (such as fighting a disease that runs in the family). Many large charities are less frugal with their money, and it can be easier with local charities to see how the money is being spent. On the other hand, I feel like the people who need the most help do not live near me, so I don’t go local.

I prefer to look for bigger issues, to look for charities that fix problems rather than apply bandaids, and to look for charities that are efficient. I’m sure there are many ways to do this.

I decided that the issues I wanted to help with were environmental issues, relieving abject poverty, and relieving pain.

I currently contribute to the following organizations:
* Nature Conservancy - rather than begging the government to make laws, these guys just buy land. And they do the research to find which purchases will make the most difference in saving habitats. And if someone is doing a good job already, they try to learn from them. These guys are not people that farmers and ranchers are afraid are going to come in and restrict the use of their property if an endangered species is found there.
* Conservation International Foundation - these guys seem similar, though I don’t know anyone who works with them directly, so I’m not totally sure. They have lower overhead costs than the Nature Conservancy.
I’ve heard that local charities tend to be much better for environmental concerns than large ones, but I haven’t done any research yet. You can better focus on a particular problem like oceans or rain forests this way.
* ACCION International and FINCA International - these organizations do microlending. It is amazing what a small amount of money can do. For example, they can lend $300 for someone to buy a sewing machine to start a business. Then as the business grows, they pay back the loan. Meanwhile, they meet with other local small business owners and give each other ideas and encouragement. Then they can qualify for another loan. For example, they can buy another sewing machine and hire someone. These are like Kiva, only the money gets paid back to the organization and re-lent, so it is a charity.
* Planned Parenthood - I think that making it easy for people to have only as many children as they actually want can help with both poverty and the environment. I looked hard to find an organization that doesn’t do anything forceful or otherwise icky (although I understand that if you are opposed to birth control, the whole idea behind this organization will seem icky to you).
* Arthritis and Cancer Pain Research Center - it’s not so easy to find a good organization to fight pain, but a life filled with pain sounds just wretched to me. I am open to other suggestions on how to address this issue. This organization seems fine, but research dollars don’t go very far. But places that dole out or teach the few methods we know so far sounds more like a bandaid than like it’s addressing the source of the problem.

One final recommendation. Use http://www.justgive.org to make anonymous donations. Then you will not get on people’s lists and start receiving mail from hundreds of organizations begging for your money. It’s distressing and annoying. Justgive does charge 3%, but this is much, much lower than the overhead expenses for my employer’s annual contribution campaign which I used to participate in, so I made the switch.

I work in the advocacy field, and I am continually impressed with the great work done by the Friends Committee on National Legislation (www.fcnl.org). They advocate for progressive causes and a more peaceful world. Your contribution can either go toward tax-deductible or non-tax deductible purposes.

I also give money to A Simple House (www.asimplehouse.org) a Catholic community in DC which exists to help the poor of Southeast DC. Both of these organizations have monthly debits set up to make it easy to support them consistently.

If you are interested in environmental issues, check out Sustainable Conservation - I think the it leverages $ better than any other 501(c)3: http://www.suscon.org/

http://www.eff.org/

These charities would appreciate your support.

http://www.warmhearts.org/

http://www.lrcompassioncenter.org/

I would recommend the following two:
http://www.heifer.org (teach sustainable farming and animal raising techniques and in so doing, are radically changing the lives of impoverished people all over the world).

http://www.kiva.org (this organization actually lets you give micro loans)