Last update: Brave New World Update
At one point, the droprate of XP Runes got rather nerfed (though it has since recovered) to the point where I thought it necessary to do an analysis on these things. So I’m gonna give you some numbers and graphs on how they work.
The best place to get runes is Underworld Madness. AFAIK, playing any level of Underworld Madness will give you either 5x 3* runes, 2x 4* runes, 3x 4* runes or 1x 5* rune. These can be any color.
Battlefield Madness will give you 4x 3* runes, 2x 4* or 1x 5* rune.
Kingdom of the Sands Madness will give you 2x 3* runes, 1x 3* runes or 1x 4* rune.
Ailing Kingdom Madness will give you 15x 1* runes, 4x 2* runes or 1x 3* rune.
Two other options for XP Runes exist: every month, you can buy a Talisman Power Up Pack from the Store for 625 Ironite for each color. They give 99 5* XP Runes, along with some Gold and Evolution Runes to power them up. XP Runes are also available in Brave New World, but given the high Sands of Time cost, farming for Runes there is not that practical.
They are also available in Skull Quests, namely the XP Material Cache & Hoard.
Approximate Rune Drops on Underworld Madness by day
Esquatcho has made a handy study on approximate rune drops here (Outdated; drops have improved since then)
Here’s the amount of gold it costs to use one rune:
1* rune: 150
2* runes: 525
3* rune: 3000
4* rune: 6000
5* rune: 14400
Here's how many runes you need to max out a Talisman (Talisman rank ups are NOT included here):
Attachment 3080
It appears that for every 2 runes you spend that match the Talisman color, you need 3 runes that don't match the Talisman color if you want to max your Talisman.
So a 2:3 ratio
Here's the rate at which a 5* Talisman levels when given (color-matched) runes
Attachment 2134
If you don't have enough runes to fully max a Talisman yet:
A level 17 5* Talisman's stats are all equal to or more powerful than a level 40 4* Talisman
A level 12 4* Talisman's stats are all equal to or more powerful than a level 30 3* Talisman
And here's a picture that shows Talisman stats at level 50:
Attachment 3824
If there's anything obvious that I missed or you want to know, just say so and I'll investigate.
Hope this helps you all.