Spells in NS are fairly uber--Epic Spells like Hellball and GR regularly do damage in the 400-500 range, but the other offensive Epic Spells aren't as useful. Negative Burst is also pretty useful (most sorcs are over 400 when Maximized when critters fail their save). However the DC for spells tends to be woefully low after about level 30 unless you put a LOT of effort into raising them, so don't expect to blind something you are fighting if you are level 36 unless they roll a 1. Many creatures also have immunity to Death Magic and Mind-Affecting Spells as well as others, so generally you are left bludgeoning them to death with IGMS, Ice Storm and Neg Burst.
Implosion is not affected by Immunity to Death Magic and Stunning Fist is not affected by Immunity to Mind-Affecting Spells.
Weapon Specializations are pretty much useless as the Tritons (best weapons in the game) have an extra umpteen-d-whatever damage added to them.
Some of the top shelf monsters have around 10K HP's, but low AC's to balance that--prepare yourself for some long battles on occasion...
Many monsters are Crit Immune (which includes Sneak Immune), but large crit ranges are still very useful.
Damage Reduction is useful on a DD Tank, but Energy Resists are (generally) not due to the amount of damage being soaked up by your gear.
Lets see...what else...
Nearly everything has True Seeing (including a lot of gear) so Move Silently and Hide in Shadows are pretty much useless in the post-epic levels.
Don't take Epic Shadow Lord...he won't last very long...nor do any summons for that matter with the unique exception of the new Starfall area item summon.
Open Locks comes in handy as does Disable Trap.
Bard Song is buffed...read in the forums for an exact table, but the long and short of it is an effective +11AC/+10AB to the party for a toon with at least 32 lvls of bard and a perform of 100.
It has been a long day at work and I needed a distraction...
Alignment changes are possible, de-leveling is not, under *any* circumstances, unless you're toon gets bugged for some reason, then you might be able to de-level if you ask very nicely.
Feats and Classes have been left alone for the most part (other than what's already been stated)--at least that's been my experience.
For shifters, Iron Golem and Risen Lord tend to be the most popular, although Rakshasa (sp) is useful too. Some items merge into your form, but I don't have that list off the top of my head.
With the addition of the new AA/Ranger arrows, archers now pwn.
If you play on Pacific, be forewarned, they haven't updated to all the new areas yet, but I hear a solution is in the works.
Persuade, Intimidate, Bluff, Appraise, etc. aren't useful. Taunt is in some cases. UMD is if you're not a magic user.
For me the magic numbers seem to be around ~800 HPs, 80 AC and 60 AB for a level 40, fully-equipped toon--if you can get there (and there's room for improvement, most certainly) then you'll do ok pretty much wherever you go, although some areas require a party no matter how uber you are. The dojo is pretty good at testing these stats for your build because Zing has most of the actual gear that you'll find in-game.
I'd start with a Dex-based Fighter of some sort for your first toon. They work well in almost every situation and will make it easier for you to learn the mod. Then it will be easier for you to build a sorc, bard or shifter, especially if you decide to gear the new character up--Warning: some gear is level retricted...Lost Paradise stuff is 18+, Enchanted City gear is 23+ and Tritons are 25+.
Unrestricted PvP action can only be found on Midwest. I highly recommend it once you've gotten a handle on things. Before then, it could just be frustrating, although I and many others have started our NS experience there.
There are TONS of stuff I'm leaving out, but I need to stop now before someone catches me...
I'm sure others will add to/disagree with what I've said, so check back for more info...
