The current security problems in cyberspace are characterized by strong and complex threats. Defenders face numerous problems such as lack of prior knowledge, various threats, and unknown vulnerabilities, which urgently need new fundamental theories to support. To address these issues, this article proposes a generic theoretical model for cyberspace defense and a new mimic defense framework, that is, Spatiotemporally heterogeneous, Input aware, and Dynamically updated Mimic Defense (SIDMD). We make the following contributions: (1) We first redefine vulnerabilities from the input space perspective to normalize the diverse cyberspace security problem. (2) We propose a novel unknown vulnerability discovery method and a dynamic scheduling strategy considering temporal and spatial dimensions without prior knowledge. Theoretical analysis and experimental results show that SIDMD has the best security performance in complex attack scenarios, and the probability of successful attacks is greatly reduced compared to the state-of-the-art.