The orthodox paradigm to defend against automated social-engineering attacks in large-scale socio-technical systems is reactive and victim-agnostic. Defenses generally focus on identifying the attacks/ attackers (e.g., phishing emails, social-bot infiltration, malware offered for download). To change the status quo, we propose to identify, even if imperfectly, the vulnerable user population, that is, the users that are likely to fall victim to such attacks. Once identified, information about the vulnerable population can be used in two ways. First, the vulnerable population can be influenced by the defender through several means including: education, specialized user experience, extra protection layers and watchdogs. In the same vein, information about the vulnerable population ultimately be used also be used to fine-tune and reprioritize defense mechanisms to offer differentiated protection, possibly at the cost of additional friction generated by the defense mechanism. Secondly, information about the user population can be used to identify an attack (or compromised users) based on differences between the general and the vulnerable population. This paper considers the implications of the proposed paradigm on existing defenses in three areas (phishing of user credentials, malware distribution and socialbot infiltration) and discusses how using knowledge of the vulnerable population can enable more robust defenses.