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I'm ready to go through my box of Thickers/alphas and purge the sets that are no longer usable. I'd like a sort of rule of thumb/guideline, so I don't spend unnecessary time dithering over each set. I should say that while I mix fonts in a multi-word title, I never mix fonts within a single word. And I'm getting in the habit of gluing them down anyway despite them having adhesive, so the fact that they're no longer sticky isn't a criteria for me. So when do I say adios - when there are no alphas left? When there are no Jeopardy consonants - R, S, T, L and N? When there's less than 20% of the pack left? Anything I've had for a decade - even if I haven't used a single letter (especially if I haven't used a single letter)? Do you have formula a to share?

I think it was Marianne that posted a LO where she used all of the unusable alpha pieces and just put them down in a block. It was really attractive.

As for purging, when I can no longer make a word out of a set, they go into a stack for mixed media. When I use them I gesso over them so I have a blank but textured starting point.

Pam C is the queen of being able to mix fonts and I wish I could do that, too. Unfortunately I'm fairly OCD.

Once all the vowels are gone, the rest would go especially if they were flat rub on or sticker letters. If they were chipboard or thicker I would keep them for mixed media or whatever clever idea Pam P. says I did with them. I can't remember! Actually I still have two unfinished projects with our initials on them in all different fonts. They made the trip so I need to do something with them.

Do you use pop dots? They are good replacements for pop dots. If not, then I would agree that when you’re out of vowels, they’re pretty difficult to use. (I do use C H K M R & Z to identify little packages I mail to the kids and grandkids - just the first initial of their names.) I will Frankenstein some letters. You can sometimes use consonants for identifying airports (CLT, for example).
I don’t like mixing fonts in a word and it’s very difficult for me to mix colors in a word - even if it’s the same font!

At this point I have so many that I'm not necessarily looking to keep them for mixed media projects. Pam C, the idea to use consonants for airport codes is good; hadn't thought of that specifically although I have done it.
For fun, I posted this question on a scrappy board that's quite active and got some good responses, so am sharing here in case they're helpful to y'all:
One gal said she figured out the consonants most often in her family's names and if they were gone - so were the alphas. Not unlike Pam C using first initials for packages - which I've often done for cards and packages for my family as well.
Someone said she purged all the glitter ones because she doesn't use them.
Someone said she keeps the numbers when she purges the unusable alphas - for birthdays, dates, Dec Daily, etc.
Someone said she uses the foam ones as pop dots (as Pam C said).
Someone said Crafty Jen Schow makes words with the leftovers right in the package so she can see what she has.
Someone mentioned an anagram finder - useless if you have no vowels left.
Someone said she fills in the missing letters of a word using stamps.
And then the usual suggestions for filling a background or using for mixed media.