The largest flash-based player that I've seen is Creative's ZEN 32GB (and the iPod touch 32GB). It has an SDHC slot, but that limits you to 40GB total given that there's nothing more than 8GB cards on the market at present.
The Zune 80 fits most of your description, but there's no mic, it uses a hard drive for storage, and (most importantly) it requires proprietary software. That said, the Zune jukebox app is definitely going to be more pleasant than what Creative offers.
Is the real concern software as a whole, or Creative's software specifically?
WMA Lossless is the biggest problem, I'd think: very few players support it. In fact, you'd have an easier time finding a player that handles Apple Lossless (i.e. every recent iPod with a screen) or FLAC (Cowon and similar). The only other player lineup I can remember off-hand that supports WMA Lossless is the Toshiba Gigabeat series, and you won't find an 80GB model even if you import from Japan.
I have been looking forever adn can not find what I want.
here is what I would like.
No required software (i got real pissed off with my Zen 16GB)
wma lossless play back
good sound quality
no HD (like that is going to happen)
When listing to music have a 25 hour audio battery life (without the screen being turned off when on hold (like the Zen))
5-8 hour video
A screen big enough to watch full lenth movies
Fits in my pocket (Archos 605 a bit big)
Has to have buttons (it can be touch as long as it has buttons becuse when its dark on the bus it is just to bright to look at)
Microphone with a gain control on the device
FM radio good to have but I really do not need it
Less than $250 (or about)
Louder sond output the my Zen 16GB
Looks do not matter
I will think of more things to add later dont worry but I need ideas about a player.