How about an extension of the Enterprise episode "Twilight"?
The Xindi manage to destroy the Earth and humanity is cast to the four winds. All human colonies are systematically destroyed, including Mars, Luna, Proxima Centauri, the Vega colony, Tau Ceti Alpha, and so on. While the majority of mankind was wiped out when Earth and the colonies were destroyed, a few thousand remained throughout space, explored and otherwise. A contingent remains on Vulcan, another on Andoria, perhaps, and still other small groups on Denobula and other friendly worlds that the Xindi would refrain attacking for fear of reprisals.
So, the human colony of Tau Ceti Alpha is attacked and destroyed via orbital bombardment in 2164, and with it the last bastion of mankind. Enterprise and the other human vessels are similarly destroyed or manage to escape the system with heavy damage. The Vulcan High Command - finally having had enough of the Xindi and their Weapon - declare the remaining humans under their protection. Likewise, the Andorian Imperial Guard pledge their support to defend the remnants of mankind at whatever cost (which should prove fairly easy considering there are so few remaining). The Xindi - having had to deal with the unchecked growth of the Delphic Expanse - finally retreat to their own sector to decide how to deal with the slow but seemingly unyielding reconfiguration of their space.
Late in 2170, the Xindi Council approached the Vulcan High Command for their assistance in repairing their space. While the Vulcans had little reason to aid the Xindi (given their annihilation of Earth and the other human holdings), the growth of the Delphic Expanse was too great to ignore. However, having developed deflector shield configurations that successfully repelled the various anomaly fields without the side effects of Trellium-D, Vulcan science ships and cruisers managed to explore the Expanse in great detail. They analyzed the Spheres, deciphered their communications link, and - despite the actions of the Sphere Builders and their Reptilian and Insectoid henchmen - collapsed the entire network and restored normal space in 2172.
In 2174, the Vulcans and the Xindi-Primates - along with the Denobulans, Coridanites and the remaining humans - formed the Vulcan Hegemony. This supposed "alliance of equals" was in fact a Romulan ploy to unite several technologically-advanced races under the Vulcan banner and eventually for the Romulan Star Empire to seize control.
Unfortunately for the Romulans, the katra of Surak was recovered from a subterranean archaeological site and placed within the Vulcan priestess T'pau. This single event transformed Vulcan and its allies, and the Romulan influence quickly evaporated.
By the end of the 22nd century, the Vulcan High Command and their allies (by this time including the Bynars, Bolians and Betazoids) have expanded their sphere of influence to include the remnants of the Sol system (where roughly 20,000 humans have settled on one of the Jovian moons in the hopes of establishing a new homeworld) as well as several former Andorian and Klingon colonies ceded them in a string of treaties ending a number of brush wars and similar incidents. Thankfully, despite their technologies, their aggression and their armadas, neither Qo'nos nor Andoria were capable of matching the power or versatility of the Vulcan combat cruisers.
By the dawn of the 23rd century, Hegemony space covers roughly 38% of what would otherwise be the Federation (and includes small areas that belong to the Klingons in the standard timeline). The Klingons and the Andorians are both lesser powers, each held in check by Vulcan space forces as well as the fact that the two races are unable to deal with each other without things collapsing into a bloodbath. The Tellarites and the Xindi-Arboreals established a trade alliance in 2192 and have colonized nearly two dozen star systems between Tellar and the new Arboreal homeworld; the Grand Nagus of Ferenginar is working to establish commercial ties with the Tellarite Confederation.
The Cardassian Union, unlike in the standard timeline, made first contact with another warp-capable species - the Vulcans - in 2207. Despite their aggressive nature, something about the Cardassian appealed to the Vulcans, and members of their diplomatic corps pressed for direct negotiations with the Detapa Council. Within a decade, Vulcan-Cardassian technological and cultural exchanges wrought a series of unexpected changes on Cardassia Prime. A renaissance began in 2217 that restored much of the glory of the First Hebitian period. Hegemony terraforming protocols restored balance to the devastated Cardassian ecosystem, and the incorporation of the teachings of Surak into their society brought to the Cardassians an appreciation of not only the Vulcans' accomplishments but of their own as well. While not a member of the Hegemony, Cardassia Prime and its planetary holdings are closely allied with the Vulcan High Command.
Deep within the halls of the Romulan Senate, the Proconsul and his allies cast their hungry eyes on Hegemony Space, the Klingon and Andorian Empires, and the Cardassian Union. The elimination of humanity proved a boon for the Star Empire, but the ascendancy of Vulcan, the recovery of Surak's katra, the marginalization of the Klingons, and the resolution of the "Xindi problem" have all confounded the Romulans' plans. Nevertheless, the whispers in the halls of power indicate that a green storm is rising...
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