Circle Thrift—South Philadelphia | Fishtown
A project of Circle of Hope and Mennonite Central Committee, Circle Thrift takes donations and sells them at low prices to raise funds for various community projects or international needs. Monthly Circle Thrift gathers donations of children's goods ad offers them for free to area families through their Baby Goods Exchange.
What they take: Everything. Including torn clothes or defected items - mark these items as "recycle" and Circle Thrift will arrange for the proper reuse and recycling.
How to donate: Drop off at one of their two locations during open hours, or if you have larger items you can call for pickup.

Cradles to Crayons—Conshohocken
Their mission is to provide children from birth through 12 living in homeless or low-income situations with the essentials they need to thrive at home, at school, and at play.
What they take: Donations of new and nearly new clothes and goods used by children of all ages. See the full list here. 
How to donate: Physical donations are accepted at their Conshohocken warehouse 24/7 using the large white storage unit next to their building. Staff are available Wed-Fri 10:30-12:30 PM. Unusually large donations should contact rnicolo@cradlestocrayons.org.

Goodwill—Multiple locations
Donations not only provide affordable access to clothing and toys, they create jobs.
What they take: Donating items that are in working condition, contain all of their pieces and parts, and are free of stains and rips is the best way to ensure that your goods do the most good. While we accept most clothing and household items, there are a few things we can’t accept – such as items that have been recalled, banned, or do not meet current safety standards.
How to donate: Visit one of their drop off locations.

Ronald McDonald House—Center City | North Philadelphia
The Ronald McDonald House offers a homelike environment for families whose children are receiving care in a nearby hospital, so they are always in need of toys to keep siblings occupied. Two houses in Philadelphia typically serve 65 families each night.
What they take: Gently used toys for the children's play area.
How to donate: Email prmh@philarmh.org to arrange donations.

Salvation Army—Multiple locations
Salvation Army, much like Goodwill, uses donations to provide affordable goods to low-income families, as well as create local jobs.
What they take: All clothing, goods, and toys.
How to donate: Visit your local donation center or arrange for a pickup.

St. Vincent de Paul of Philadelphia—Germantown
Their mission is neighbors helping neighbors. They serve those in need of food, shelter, clothing, transportation, and emotional comfort.
What they take: All clothing and shoes, as well as games and toys, baby items with the exception of cribs (and other household items).
How to donate: Their GreenDrop service picks up from you, but donations must be 50 lbs or less. Schedule a pickup here.

Sunday Breakfast Rescue Mission—North Philadelphia | Penndel, PA
The Mission operates two thrift stores in the Philadelphia region. The combined efforts of the thrift stores generate 18 percent of the annual income to provide meals, shelter, programs, and services to families in need.
What they take: Clothing, games, and puzzles.
How to donate: Donate during regular business hours, Mon-Fri 10 AM-4 PM, Sat 10 AM-5 PM.

Photo via Cradles to Crayons.