Once you plug long term storage onto your Prometheus, do you really need the main Prometheus instances anymore?

Here’s an article about this idea: https://datadrivendrivel.com/posts/rmrfprometheus/

You can substitute the Grafana Agents for OTEL collectors as well.

While Grafana Agent uses less resources than Prometheus, there is more optimized Prometheus-compatible scraper and router exists - vmagent [1]. I'd recommend you giving Grafana Agent and vmagent the same workload and comparing their resource usage.

P.S. Prometheus itself can also act as a lightweight agent, which collects metrics and forwards them to the configured remote storage [2].

[1] https://docs.victoriametrics.com/vmagent/

[2] https://prometheus.io/blog/2021/11/16/agent/

That's just kicking the can over to an object storage API instead of managing disks.

And comes with all the downsides of Prometheus as well

Could you pelase elaborate more on "comes with all the downsides of Prometheus"?

Or, you can use Thanos, the de-facto standard with the biggest OSS community.

Thanos/Mimir community doesn't help to resolve configuration routine or even bigger resource consumption for a huge setup.

Bigger resource consumption of what exactly? Leaf Prometheus instances or the Thanos/Mimir stack compared to VictoriaMetrics? Have you seen a large scale migration between the two, with actual numbers?

A few of interesting real-world large-scale migrations are highlighted at https://docs.victoriametrics.com/casestudies/