This is a question that I have spent a ridiculous amount of time pondering.
My conclusions so far are this:
Single node application systems are by far the most reliable and manageable from a business logic standpoint. At no point does spreading a problem across more than 1 computer make that problem easier to solve.
If you are concerned about latency, you need to get really abstract with your problem and ask what is even possible in information theoretic terms. If you are truly constrained to 1 serialized, synchronous context (i.e. a competitive counterstrike match or a stock exchange), there is little you can do to alleviate the root problem as your users get further from the server. You can certainly look at using some consensus protocol like multi-paxos, but then your transaction latency goes from microseconds (if you were clever) to milliseconds, representing orders of magnitude slowdown in the typical case.
The best solution I can come up with is a synchronously-replicated append-only log store which is utilized in a primary/sync-witness/async-witness/... configuration. The first tier of resilience would be synchronous and provided by a set of witness nodes which must ack as a majority to progress primary. These nodes would ideally be within 1-2ms of the primary. The async witnesses could be in orbit and/or on mars. These are more about extreme geological disaster recovery. The witness nodes would also use a separate consensus protocol to decide when the primary needs to be taken down and replaced with a sync (or god forbid async) witness. They would be able to elect an emergency leader separate from the primary who would be authorized to stop the bad primary in the hypervisor, and edit any relevant DNS records to ensure traffic stops hitting the bad system.
For the customers I work with, it is wayyy easier to build & sell a system that operates on a single box with sync replication + manual failover. Our customers are tolerant to production having a brief outage for a few minutes during the business day. Especially considering the fact that I have still never had to do this exercise in a production setting. The hardware we run this stuff on is so ridiculously stable.