[Bushmaster]

John Cena losing an I Quit match, Undertaker losing to an undefeated rookie at mania (let's say Ryback) or Kofi beating Randy Orton for the wwe title.

 

[Patrick Bateman]

Kofi beating Orton for the wwe titel.

 

[Johnny_XTREME]

What a weird question. Anyway, I'd say - Cena losing "I Quit!" match. After that Kofi beating Orton for WWE Title and least likely to happen is Undertaker losing to anybody, especially some rookie at WrestleMania.
Though probably none of those things will happen, at least in near future (talking 'bout Cena's one).

 

[Joshi]

If "screwjobs" are taken in account then Cena losing an I quit match.

 

[A-C-P]

Kofi winning the WWE title from Orton

 

[Warren Zevon]

John Cena losing an "I Quit" match. I could see it happening for character development purposes if the mythical heel turn ever happens.

 

[Jobberwacky]

I'd say none of these are ever going to happen. Most likely to happen:

Cena says I quit, extreme circumstance, major character progression.

Kofi bts Orton for WWE title, extreme circumstance, run of injuries/retirements. WHC yes, WWE no.

Taker loses streak, loses it to upcomer with undefeated streak, extreme circumstance, hope it never happens.