Comment Salesforce.com (Score 3, Informative) 186
Salesforce.com is a pretty amazing platform for doing CRM that goes well beyond just donor management. As others have mentioned, the Salesforce Foundation makes it available from free-to-darn-cheap. It has good Outlook/Office integration, and unlike most other solutions Salesforce has an really solid Web Services API that makes it possible to integrate with all kinds of other systems, notably including Plone, the open-source CMS system that many nonprofits use.
ONE/Northwest, the nonprofit I work for, has done a ton of work in this area, and has had great success at delivering powerful, easy-to-use solutions to mid-sized environmental nonprofits.