I've been playing around with increasingly esoteric builds in my Dredmor games, so I thought it would be nice to share:
Man-At-Arms - Swords, Maces, Axes, Dual Wielding, Berserker, Master of Arms, Piracy.
This build is all about weapons. It's viable in RotDG moreso than in vanilla DoD, because getting amazing equipment is much easier with the expansion levels in place.
Taking multiple weapon skills seems a bit silly, since the bonuses for each weapon only apply if you are actually holding a weapon of that type. But you can use the area attack for each weapon regardless of what you are holding - and therein lies the magic. Kicking ass with multiple AoE weapon attacks every 2 or 3 turns is pretty boss. You could take Staves instead of Berserker, just to complete your suite, but I found it pretty unnecessary.
Piracy is there for survivability reasons - Mists of Corsair will save you from big battles, and gives you a nice +20 dodge. You will rely on heavy armor - Master of Arms starts you off with an iron breastplate, which is a huge early advantage. All of the warrior levels means that your damage and HP should be high enough to carry you through the first couple levels without too much trouble. Floor 4 is where your elemental resistance start to be a problem. This isn't a build which can waltz through any thing, but it has a certain simplicity which makes it appealing.
The name is a He-Man reference, for you younglings.
Indecisive - Shield Bearer, Psionics, Magic Training, Burglary, Archeology, Big Game Hunter, Emomancy.
This build makes use of some odd synergies between some utility skills - plus a whole lot of bonus experience via Archeology, BGH, and Burglary. It uses 2 warrior skills, 2 rogue skills, and 3 wizard skills.
Shield Bash grows in power with Magic, so it becomes a pretty good offensive go-to attack. Abusing Psionics has always been strong, so an early point to grab PsychoKinetic Shove is probably a good idea. Emomancy is great for the first 3 skills - but you probably don't need anything beyond that, at least not for a long while. My Chemical Explosion scales pretty well with only modes Magic Power, so use it frequently.
Big Game Hunter is something you can safely ignore for the most part - it gives a ton of bonus XP without a single skill point invested. It's nice to get your diggle hounds eventually, but they are only as good as your ability to kill things, once "things" are distracted away from you.
If you've wanted to try a strange hybrid, this one is the best and the strangest.
Asking For It - Axes, Dual Wielding, Archery, Artful Dodger, Viking Wizardry, Smithing, Tinkering.
This build is focused on achieving the "I didn't ask for this" achievement, which requires two clockwork chain-axes, power limbs, and a clockwork bolt-thrower. You are role-playing a cyborg, which makes the electrical buff in Viking Wizardry thematic. Viking Wizardry, Dual Wielding, and Archery are low importance skills - level up your axes first, get two levels of Dodge for Knight's Leap, and then focus on Smithing.
This build can have a bit of a rough start - but once your Smithing & Tinkering are in play you should be able to do huge damage at range and in melee range. Your inventory will be a mess, but if you keep your eyes on a few key prize items you should be able to start your cyborg-rampage by DL5 or so.
I'm a Wizard, Too! - Staves, Fleshsmithing, Astrology, Magic Training, Ley Walker, Alchemy, Demonologist.
This build makes use of Fleshsmithing and Astrology - the least-popular magic trees. Demonologist is the tree you want to take only to level 3, but no further, for the awesome Celestial Circle. Getting a point into Ley Walker and Astrology will help you deal damage in the early game, and of course getting your Alchemy Skill up to level 5 will give you excellent potions, weapons, and Magic Power.
The traditional problem with both of these magic trees is the fact that their top AoE powers are so dangerous to the user. Celestial Circle does a great job of mitigating that risk, and Ley Walker gives you tools to keep your Mana up while you do it. You'll never be more efficient than the mathemagic-promethian guys clearing out the dungeon blindfolded, but hard-working wizards can find success. Probably. Hopefully?
Pew Pew Pew! - Axes, Archery, Artful Dodger, Perception, Burglary, Smithing, Tinkering.
This build is for shooting with. Smithing is just for double ingots - which means double arrows made from those ingots. (Taking one level of smithing for the +1 Traps might be reasonable). Axes is just there for the critical chance increase - which applies to your fired arrows as well! Burglary gives free arrows from vending machines - and has all the standard amazing escape options later on.
But to start, you need to just focus on leveling up Archery, and Tinkering. Maximizing both of those ASAP is really all you need to focus on. You will probably end up with lots of arrows in your inventory - don't be afraid to use the bad ones freely! You need steel to get the best crossbow, but other than that you should pretty much avoid crafting anything other than arrows - just for your own sanity!
By DL2, you should have establish a pattern of "shoot once, melee once" against most enemies. Elemental arrows are very valuable, because some enemies just laugh off your piercing damage - and those are largely the same foes who will laugh off your melee hits. Elemental arrows are your solution there.
When you find a room which allows you to create a vending machine, I suggest Arrows over crafting. It's nice to horde your Cruelly Barbed Arrows, since those are the ones you'll be crafting at Tinkering level 4+. Goggles let you start making arrows at Tinkering 3, if you are desperate to put skill points other places. (Note that the goggles themselves require level 4, but sometimes you get luck in the shops.)