So, I've picked up 14.1 and am trying two of my favourite combos: Draconian Transmuters and Demonspawn Assassins.
I'm not doing very well in the early game and I suspect part of my problem is skill choice. For the DrTrs I'm focusing on Unarmed, then Transmutations or Dodging. For the DsAs I'm doing Stealth, then Dodging, a bit of Short Blades and then more Stealth.
I've been training only one skill at a time (easier to keep track of and it goes up faster) but don't really have a good idea of when to switch my focus or which skills to prioritize. This usually sinks in when hard-hitting things start showing up and my EV is still worthless. I also intend to invest in Fighting and Inv/Evo depending on god choice but rarely get that far.
Tips?
Concentrate a lot more on your offensive skills. For both assassins and transmuters, they're rather 'utility' based classes to start with, so they need some good offensive training. For transmuters, you definitely want to get unarmed good, with just enough put into transmutations to get the next spell working. As you won't need to spam cast stuff, it doesn't matter if things are at around 15% faliure rate. Assassins need to train throwing for darts and get short blades up as well.
I'd spread your xp around as well - assassins could definitely have stealth, short blades and dodging on and transmuters could go with unarmed, dodging on 'strong' (double press so it lights up) and transmutation on low.
Although I hate to say it, have you tried some of the easier classes, especially for assassins? Spriggans and kobolds are a lot better suited, and getting them off the ground first will help a lot. Transmuters are generally challenging and need a lot of use of consumables/tools to get them off the ground.