Alterando o app.config

Configuration config = ConfigurationManager.OpenExeConfiguration(ConfigurationUserLevel.None);
AppSettingsSection configSection = config.AppSettings;

try
{
    if (configSection != null)
    {
        if (configSection.IsReadOnly() == false && configSection.SectionInformation.IsLocked == false)
        {
            configSection.Settings["myKey"].Value = "newValue";
            config.Save();
        }
    }
}
catch (ConfigurationException ex)
{
    MessageBox.Show(ex.Message, "Configuration Error", MessageBoxButtons.OK, MessageBoxIcon.Error);
}