The TB20/TB21 will essentially match a Seneca up to any altitude, turbo for turbo.
A TB20 has a
20k ceiling and a TB21 has a 25k ceiling.
I don't think a Seneca (with boots) has a greater weather penetration capability than a TB20/21 with full TKS. Where would it come from? TKS is a damn good system. It has more redundancy (2 engines obviously, but also 2 alternators, etc) but that is a very different argument.
Obviously if you want a spare engine, etc, and are happy to pay for it then there is no argument and basically you are paying extra due to your different attitude to risk.
But I think many pilots think that a twin is somehow better able to penetrate crap weather. It usually is but only by virtue of equipment more often fitted to twins than to singles. But look at say a Cessna (Lancair) 400 - two alternators, de-ice, fully dual buses, etc.
Also, a twin has approx 2x more stuff to go wrong. The vast majority of problems on a plane are minor (thankfully!) and on a twin you will get a lot more of them. GA build quality tends to be somewhere around a Vauxhall Viva, and the avionics are designed mostly by dropout "engineers".
If you maintained a single to a zero defect tolerance (as I do with mine) or a twin (the same), the twin will cost you 1.5x to 2x more - for the same airframe age!
Now factor in the chance of the twin being older (because a given budget will generally acquire an older twin than a single) and you are looking at a significant operating cost difference.
Then add in the extra fuel
