Nagios for me (and a coworker). Monitoring around 200 Linux, Windows, Solaris, and OS X hosts. As far as the pain of configuring it, that's somewhat reduced with use of object templates. Example (from host-types.cfg):

define host{
        use                     generic-host
        name                    router-switch
        check_command           check-host-alive
        max_check_attempts      20
        notification_interval   240
        notification_period     24x7
        notification_options    d,u,r
        register                0
}

define host{
        use                     generic-host
        name                    dummy
        max_check_attempts      20
        notification_interval   240
        notifications_enabled   0
        register                0
        address                 127.0.0.1
        notification_period     none
        }

We generally make one configuration file per room we have systems in. Example (from ch314.cfg):

define host{
        use             generic-host
        name            ch314-host
        parents         ch314-switch
        contact_groups  admins
        register        0
        }

# Individual host definitions
define host{
        use                     dummy
        host_name               ch314-switch
        alias                   CH314 Switch
        parents ch302-switch
        }
define host{
        use             ch314-host
        host_name       ch314a
        address         A.B.C.1
        }
define host{
        use             ch314-host
        host_name       ch314b
        address         A.B.C.2
        }
define host{
        use             ch314-host
        host_name       ch314c
        address         A.B.C.3
        }
# Service definitions
define service{
        use             ping
        hostgroup_name  ch314
        contact_groups  admins
        }

define service {
        host_name               ch314b, ch314c
        service_description     SSH
        check_command           check_ssh
        use                     generic-service
        notification_interval   0 ; set > 0 if you want to be renotified
        contact_groups          admins
        }

# Dependencies
define servicedependency {
        host_name                       ch314b
        service_description             PING
        dependent_host_name             ch314b
        dependent_service_description   SSH
        execution_failure_criteria      c
        }

# Hostgroup definitions
define hostgroup {
        hostgroup_name  ch314
        alias           Clement Hall 314
        members         ch314a, ch314b, ch314c, ch314-switch
        }