Most charities are classified by the IRS as 501(c)(3) organizations, and as a result, gifts made to them are eligible for a tax deduction. Always check with your tax advisor to learn to what extent you can use the deduction for the current tax year.
Follow your passion: helping the homeless, sharing with returning soldiers, feeding the hungry, supporting the visual arts, giving to your alma mater, whatever you care about, that is what will make the difference for you and for your city or town.
Once you've figured out your passion investigate before you give. Look at www.guidestar.org or www.charitynavigator.org to learn more about the groups you think you want to support. As a rule of thumb, when looking at expenses, if 75% or more is spent on programs that is a positive, and 15% spent on administration and 10% on fundraising, you'll be looking at a well managed organization that is making a difference.
Watch out for unsolicited phone calls, emails, or letters. These may be phishing expeditions that could lead to identity theft. Investigate, make your decision, and then make your gift. If you really love supporting the groups that speak to your heart and your mind, then become an annual donor, attend events, and be an ambassador for the organization and its good works.