How about something involving a far more fundamental change?
Thanks to Annorax and his weapon ship, all life on Earth is erased from history. Now what?
Each power existing in the altered timeline would clearly have developed in a similar fashion to the point that they should have encounterd mankind. Canon sources set these dates as follows:
Vulcans - 2063
Klingons - 2150
Andorians - ~2150
Tellarites - ~2152 (?)
Coridanites - ~2151
Denobulans - introduced by Vulcans some time prior to 2150 (likely late 21st century)
Obviously this prevents the conflict with the Xindi and the Suliban Cabal, and interactions with dozens of other races as well.
So the Vulcans remained isolated pretty much to their own planet as they seem not to colonize many other worlds. The Klingon Empire expands unchecked by humanity, spreading to, say, two dozen star systems by the end of the 22nd century. Andoria and Vulcan continue their cycle of small wars and dodgy peace throughout the 22nd century, culminating in a war that devastates Andoria and the Imperial fleet.
The Romulans continue their infiltration of Vulcan society, working to direct their cousins toward D'era and away from Tu'Surak. This plot ultimately fails when Surak's katra is recovered in 2155 by T'Pol after the death of her mother. When the katra is transferred to T'Pau, Romulan influence - while never discovered as such - is quickly marginalized and eventually ends altogether.
Fragmentation among the Xindi due to the influence of the Sphere Builders leads to a four-front war between the Primates and Arboreall, the Guardians and Reptilians, the Insectoids, and the Aquatics as a friendly neutral to the mammalian alliance. The Sphere network is destroyed in 2163 when an Aquatic vessel sacrifices itself, crashing into one of the control Spheres and collapsing the network. The Reptilians are systematically hunted to extinction by the Primates and Arboreals, and the Insectoids establish a new homeworld beyond Xindi space.
A union between Vulcan and Xyrillia (with Denobula Triaxa, Coridan and Breen as junior members) creates a stable interstellar society in 2189, but few other warp-capable races express much interest in membership or even formal contact beyond the occasional trade agreement. The Deltans are an associated race, but keep mostly to their own world.
Betazed is swept by a plague in the late 22nd century that kills over 40% of the population. The unfortunate incident was actually the result of tampering with their history courtesy of the Cabal and their 26th century masters.
Bynaus becomes the center of computer technology for much of the quadrant, and lucrative contracts with the Ferengi Trade Consortium ensures their technologies are found well beyond their homeworld.
The Ferengi, ever eager to make a profit, return to Valakia in 2160 and sell them a cure for their genetic degradation (developed on Tandaar Prime with the assistance of Bynar medical expert systems).
Likewise, the Valakians acquire warp drive and fusion technologies from their Ferengi friends, and they quickly colonize the fourth planet in their system, eventually relocating the Menk population in its entirety. Thanks to their adaptability, the Menk thrive on the barely Class-M world, eventually building an Iron Age society with various modern supplements, courtesy of their Valakian patrons.
The Axanari conquer a series of systems populated by several Stone and Bronze Age societies. They establish the inhabited planets and client worlds and install military governors to manage their holdings. While some (mainly the Vulcans) are concerned by this, no one takes steps to prevent it until the Klingons go to war with Axanar in 2202. The war lasts for nine years and ends in a Pyrrhic victory for Qo'nos, whose fleet is in tatters. The Emperor is unseated by the Great House of Duras, and the Klingons consolidate their remaining assets around Praxis, their key energy production facility. So long as Praxis remains secure, the Klingons have nothing to worry about...
The other races of the Alpha and Beta Quadrants influenced by humanity remain relatively unchanged despite the lack of contact with mankind, though the natives of Sigma Iotia II instead remade their society in the image of 17th-century Vulcan when a copy of The Teachings of Surak was discovered in the wreckage of a Vulcan survey vessel c.2168. Vulcan explorers were pleased (or at least as pleased as Vulcans can get) when they eventually rediscovered Sigma Iotia II in the mid-23rd century and brought the Iotians into their union shortly thereafter despite their lack of warp technologies.
The late 23rd century fell into chaos when the Klingon moon exploded and Qo'nos declared war on the Xindi-Primates and their allies in a desperate grab for power and resources. They were rebuffed thanks to aid from the Valakians and Malurians as well as several companies of Nausicaan mercenaries. The Klingon Empire fell in 2299 and was rebuilt from scratch when it was bombarded by the Diaspora Device, a Xindi prototype device that scoured clean a planet's ecosystem and remade them into completely new, Xindi-compatible worlds.
This same technology was stolen by Ferengi merchants and sold to the Suliban Cabal, who used it against three Tandaaran worlds before they were defeated. A convoy of non-Cabal Suliban also acquired the technology and used it to revitalize their ecologically-devastated homeworld, and Suliban throughout the sector began returning to their homeworld in the early 23rd century.
The Tellarites fell afoul of the Axanari (before their defeat at the hands of the Klingons) and were forced into exile when their world, Tellar, was destroyed by fusion weapons detonated in their atmosphere. They wandered the galaxy in small convoys of ships until the mid-23rd century, when the 250,000 survivors were granted sancutary in Vulcan union space and settled on various worlds therein.
Without mankind, the future is unclear. While removing Earth from the equation returned the Krenim Imperium to their greatest level in history, it caused unimaginable havoc in the Alpha and Beta Quadrants. Annorax retired his weapon ship and returned to his wife where he leads a life filled with happiness and contentment.
mactavish out.
Our country's past progress has been the result, not of the mass mind applying average intelligence to the problems of the day, but of the brilliance and dedication of wise individuals who applied their wisdom to advance the freedom and the material well-being of all of our people.
-Conscience of a Conservative, Barry Goldwater