I hope they can get like 300 some slots.

254 is a limitation brought about by using one byte to store resource IDs - that's 256 possible values of the byte, -1 for oblivion.esm, and -1 for your save file. There's no reason to increase this, but at the same time, there's little reason not to.

The next step up from 1 byte is, obviously, 2 bytes, giving a total of 65536. Or, rather, 65534, with one taken off for Skyrim.esm, and one taken off for your save file. However, I doubt any among us are counting.
So, the situation will either be as it was before, or effectively unlimited.

Being optimistic, one would hope that mods will be less necessary than they were with Oblivion.

I'm sure I'll be adding plenty of mods ... eventually. But if the devs have listened to the feedback from Oblivion, then there should -theoretically at least - be less needs for mods which 'fix' the game. And I think there are signs from Fallout 3 that things like the levelling system, game balancing and such like should be more refined. That should leave things such as adding quests and faction mods, together with the inevitable graphic overhauls for the mod 'slots'

Several thousand (or more) would be lufferly. :rock:

Yeah. The mods I use for morrowind are graphical enhancers and an unofficial patch, as well as a levelling mod. For Oblivion, I had to use countless mods. Well, about 15.