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To me, the key is the synergy between the speaker and the cabinet. A good sounding speaker can be awful in the wrong cabinet, and vice versa. When I design a new amp, the cabinet design and speaker choice happen together.
Back when I designed the Comet amp, in the 90s, I remember building literally more than 100 test cabinets to get the sound I wanted, and had a custom speaker commissioned for that design as well.
Nowdays, I have enough experience from past work that I can usually get in the ballpark on the first few test cabinets. I still begin by designing the cabinet. After tuning the cabinet through a few iterations, with various speakers, the speaker choice becomes fairly obvious. Once the speaker choice is made, I’ll run through a dozen or so more test cabinets to work out the fine details, and settle on the final design.