I suppose the answer varies depending on the growth stage of the startup.
Also varies depending on product, which might be a...
1) Front facing Website
2) Membership Website
3) API
Each have their own unique characteristics.
In general though, all systems bottleneck around disk i/o, so if you have a database heavy application, ensure you have someone who understands how to design tables for extreme speed.
And if you still require more speed, run a memory resident database, which must...
1) Sync from disk to memory when database server starts.
2) Periodically sync from memory to disk during runtime.
3) Do final sync, when ever database server stops, to bring disk backing store consistent.
Memory resident databases are a bit tricky + produce blazing fast throughput.
