Important NPCs are invulnerable, like Oblivion.
You might close off some smaller sidequests, but the folks necessary for the main story (for instance) have a tendency to be "incapacitated" from "killing" blows.
So feel free to go nuts.
Interestingly, NPC allies behave a little different, even if they are non-essential (and thus ripe for killing). When they get reduced to below 0 health, they revert into the "yield " state, which usually means enemy NPCs stop focusing on them to come after you instead. If they get hit while in this state, they will die.
Additionally, you cannot put them into this state - your attacks will directly kill them.
Absolutely.
Skills
Illusion synergises well with sneak as invisibility does not gaurantee not being detected. The CC spells are also very useful, allowing you to control situations that would otherwise overwhelm your squishiness. Silent casting will be vital, so get it asap.
Destruction will be tricky without deep magicka reserves until you start to enchant your own stuff to reduce cost. But Impact will work beautifully for single target assassinations. With silent casting, I believe you could also use runes for some fun, though on master they will quickly lose effectiveness. I would stick to one element to save perk points (perhaps shock as a useful rarely-resisted element), and don't bother with master level perk. This will be a useful tree against dragons.
Restoration is moderately useful with the respite perk, allowing you - in conjunction with light armour stamina regen bonus - to spam dual wield power attacks all day long. I would not worry about the perks above adapt. Get respite, the magicka regeneration perks, and possibly the "auto heal on zero death" perk that can help out if you are smacked around when dual-wielding.
Light armour is great, and will give you survivability that most mages don't have. It also takes up far fewer perks than Alteration.
I would skip conjuration perks completely, unless you wish to use bound weapons as a role play. You may ultimately wish to level it to 90 at some point in order to provide a non-smithing source of Daedric weapons (see smithing below), and if so don't rush on it until you need to level other skills up to level in general (high 30s onwards). Alteration has few uses in this build.
Enchanting will be useful, allowing you to supplement your lower magicka with regen and reduce costs. Don't bother with -100% cost on any given skill tree, as you will probably only use destruction as a filler against mobs and dragons but if you use it a lot against high level single targets then consider -100%, as the Expert level spells are expensive. I would aim for some +magicka regen (or +magicka - calculate which is more effective given your base magicka) as that can be used for all your magick trees, and you will be using them all not just 95% destruction like in pure mage. Possibly some reduce cost for illusion. All other slots for boosting your melee and resistances. Restoration is fine without reduced cost.
Smithing is great - but you may not feel like role playing it. Depends on your target equipment, but you could make do with steel smithing and the enchanted item smithing perks. You can get daedric weapons through the Mages guild, so don't feel obliged to perk up smithing.
Alchemy complements both skill sets well.
The Beginning
Don't spread yourself too thin to start off with. I would work on illusion, sneak and one-handed until you can comfortably stay hidden in shadows and get silent casting perk. From there you can start on destruction up to Impact, to have a useful fall-back of dual-casting firebolts (it can interrupt dragons and nasty bosses), and get restoration to apprentice level. I would then work on getting illusion to 75 and sneak till 60 for backstab bonuses. By this point you should be able to flit in and out backstabbing and skirmishing, using Invisibility as a means of getting back into cover.
Quests
You will not be locked out of any, and can complete Thieves guild, DB and Mages guild. They all work well together. Thieves guild and DB synergise well, and Mages guild unlocks some tasty equipment.
From here, you can choose. I would work on your sneaky sneaky and melee skills, as you will already have the main utility from your skill sets.
Use illusion to ensure you don't get hammered too much, and don't be afraid to go invis and hide. Your main advantages over a pure stealth character are your much better flexibility when detected - so use these advantages.
Hth =)
EDIT: stats: ymmv but I have had good sucess with balanced melee/mage with 2:1:1 health:stamina:magicka. I leave stamina at 150 (maybe 200 if going dual wield).
EDIT2: added link to find out if +magicka or +magicka regen, as per the paragraph on Enchanting. added link for Mage's guild and daedric weapons
Best Answer
The UESP wiki, 'Quest Timing' article has a detailed list of quests (and notes about those quests) that will have a significant impact on other quests and the game, in general. Some of them are due to bugs, and some are because they are designed to be that way.
It also recommends if a quest has to be done early or be postponed before/until another quest has been finished or another game event has happened, to prevent bugs or a negative impact on other quests, or the game.
The whole article is too big to be included here. I'll be adding some of the most notable quest categories and the quests under those categories related to your question:
Quests to Do As Soon As Possible
Blood on the Ice
Why: The Necromancer Amulet is a Legendary-quality item very useful for low-level spellcasting characters, especially those interested in Conjuration, and can be sold for a lot of gold for a low-level character. There are numerous glitches associated with this quest, and the best fix is to start the quest as soon as possible and complete it all at once.
The Forsworn Conspiracy and No One Escapes Cidhna Mine
Notes: ...if you side with the Stormcloaks in the Civil War and if you complete Forsworn Conspiracy before Compelling Tribute and then wait until after Compelling Tribute to start Cidhna Mine, it will become unavailable permanently. It is also possible to have the same effect result from completing Forsworn Conspiracy, then completing Season Unending before Cidhna Mine, even if you have not joined the Stormcloaks.
Quests to Save for Later
Dragon Rising
Why: Completing this quest early ensures a large number of Dragon Souls by exploring, if the player is capable of surviving the dragon's attacks.
Why not: After completing this quest, Skyrim will be full of dragons. Deferring it until you're in the mood to fight dragons lets you explore the world in relative peace and allows you to learn Words from Dragon Lairs more easily. Note that starting the quest will not cause dragons to appear; only after killing Mirmulnir will dragons start spawning.
Joining the Stormcloaks or Joining the Legion
Why not: Joining either the Stormcloaks or the Legion removes access to all the opposing faction's camps and causes "random encounter" fights to occur. Capturing towns has been known to break certain quests.
Quests that Conflict
Why: During Lost to the Ages, you are required to trek through Raldbthar, where Alain Dufont lives. If you kill him before starting Mourning Never Comes, you cannot kill Nilsine Shatter-Shield for the bonus reward in that quest.
Why not: Alain only becomes hostile if you attack him, he won't defend the other bandits in the area. You can kill all the bandits but Alain, and complete Lost to the Ages without affecting Mourning Never Comes. Also, Mourning Never Comes is only available if you choose to join the Dark Brotherhood; if you choose to destroy them, you will never be given it.