Esposito and Ryan would be really affected. They're close to both Castle and Beckett. They might feel torn between the two. Esposito, with his tough - guy exterior but soft heart, would probably try to mediate at first. He'd be the one to say 'Come on, you two can work this out'. Ryan, being more of the calm and rational one, would likely analyze the situation and try to figure out where it all went wrong. But if the break - up is final, they'd have to choose sides in some ways, like who to hang out with on a Friday night.
For the other friends in their circle, like Lanie, the medical examiner, it would be a shock. She'd be the one to offer a shoulder to cry on for both of them. But at the same time, she might get tired of hearing about their break - up all the time. She might encourage them to move on and find new relationships, but deep down, she also hopes they can work things out because they seemed so good together.