I run an Alexa top-2000 website. (Mangadex is presently at about 6000.) I spend less than $250 a month. I have loads and loads of thoughts about what they could be doing differently to reduce their costs but I'll just say that the number one thing Mangadex could be doing right now from a cursory glance is to reduce the number of requests. A fresh load of the home page generates over 100 requests. (Mostly images, then…
Do you manage to get as many buzz-words and OSS products into your system as they do? :) In general the less moving parts you have in a system the more reliable, secure, efficient and cheaper the system becomes. In their case they run a site that is probably under constant attack by the "hired goons", so they're going to need to have more moving parts than others. Plus they will want to optimise for minimal developme…
That's taken care of by the DDoS-Guard system they placed fronting their infrastructure. The design of their system has to take this into account, but that is mainly on a IP and DNS level. The design of their stack behind the loadbalancer is mainly driven by their functional and non-functional requirements, rather than by the need to prevent DDoS attacks.