Earlier quoted context omitted.
Perhaps the hardware cost would be higher with one big mainframe, but there could be many subtle advantages that would combine to reduce the overall cost, since personnel costs make up a huge chunk of total opex. I don't have enough experience to say whether having the entirety of Twitter sit in one really big metal box would be perceived to be sufficiently advantageous or not.
I think there are several TCO issues you'd run into here: - vendor lock-in: anyone who has worked at a shop running Sun SPARC machines when they got purchased by Oracle can speak to the pain involved with negotiating software licenses or hardware support contracts with the Only Game In Town. - the price/scarcity of mainframe talent: you're going to have to pry IBM z-series experts away from banks who are paying 50-10…
Whether or not removing several intermediary layers of abstraction, and the commensurate 100x (?) boost in efficiency, between users tweeting a hashtag and the actual electrons vibrating, is worth taking on the significant constraints you've enumerated.