1. When Runes Spawn
Runes spawn every 2 minutes (starting from minute # 2), replacing those that have already been taken.
This means that a rune spawns every even minute, starting from minute number 2. If a rune has not been taken, a new rune won't spawn.
According to my observations, the type of rune that spawns is COMPLETELY random and the area at which a rune spawns is also COMPLETELY random. You cannot predict whether it will spawn at the North or South, and which rune it will be.
There are several ways to keep track of when runes will spawn. The easiest way is to use your game clock. Open your score board, and use that clock to determine when a rune will spawn.
The next way requires you to use your gold on Observer Wards. Place an Observer Ward in one rune spot, and when a rune is set to spawn, look at the rune area where you set the Observer Ward. If there is a rune, then that is where the rune has spawned. If there is no rune there, it must mean that a rune has spawned in the other location.
An alternative is to check both spots. However, this might take long and it might not be worth it to lose EXP and gold. For this reason, I suggest using Observer Wards.
2. Getting Two Runes at Once
This is possible. What you must do is pick up a rune more than 5 seconds before the next rune is set to spawn. This means that you must pick up a rune at X:54 or before. Replace X with an odd number. If you do this correctly, another rune will spawn at Y:00 (replace Y with an even number). If you pick the next rune up, you will have buffs of both the runes.
However, if you pick up a rune at X:55 or after (replace X with an odd number), you will get the buff of the rune you picked up, but a new rune won't spawn till the next 2 minutes. I will use an example to show you this.
Example: Success of getting 2 runes at once
Say it is 7:30 minutes into the game. I go into the river, and I see a rune. I want to have 2 runes at once. Therefore, I pick up a haste rune at 7:50, then a DD rune spawns at 8:00. I pick up the DD rune, so now I have both the buffs of Haste and Double Damage.
Example: Failure of getting 2 runes at once
Say it is 7:30 minutes into the game. I go into the river, and I see a rune. I want to have 2 runes at once. However, I pick up the rune at 7:56, then a new rune won't spawn at both locations at the 8:00. Why? Like I stated above, you have to pick it up more than 5 seconds before. If I wanted to get 2 runes, I should have picked it up at 7:54 or earlier.