Roughly the same here: Big Sur 11.1 on MBP, 16'', 2019 Left click either from trackpad or external mouse often does not reach the application. The former focused window LOSES THE FOCUS on the click. Behaviour is often seen in safari and chrome, but also in other windows e.G on clicking the topleft red dot to close the window. Window does NOT close, just loses focus. This is VEEEEEEEERYYYYY annoying! One more thing: in safari, the effect seems to be object-specific: on the amazon-startpage, i can leftclick on any offered item, but i cannot leftclick on 'Prime Video' (Top Left). The Frame moves to 'Prime Video', when the mouse hovers over it, but on the click, the safari window loses focus. (Though shown marked in the window list...)