Spencer was the guy who started it all. He was obsessed with immortality and essentially wanted to create a new master race of humans with himself as a god to rule them. For this purpose he studied the Progenitor virus as he believed that was the key to becoming immortal and create superhumans. All of the viruses that were later created (T, G, T-Veronica, T-Abyss, T-Phobos, Uroboros and C) were derived from Progenitor so they can all be traced back to Spencers work. To him these viruses were just byproducts though, he wanted to create a supervirus that would make him a god not a monster. He formed Umbrella (along with Edward Ashford and James Marcus) in 1967 to mask and finance his viral research.
He was also initiating Project W, which was designed to provide him with a first batch of superhumans that would be the first of his new imagined world order. To that end he captured hundreds of gifted children, brainwashed them, injected them with Progenitor. Those who survived were brainwashed again and given the surname Wesker. later they were given a new experimental virus to make them superhuman but only two of the candidates survived that - Albert and Alex. Albert later went rogue and turned on Spencer in 1998 (RE 1) so after the collapse of Umbrella in 2003, Spencer only had one ally left : Alex Wesker.
The T-Virus was created by James Marcus in 1978 but when Marcus became too ambitious, Spencer had him killed in 1988 by Albert Wesker and William Birkin took over the T-Virus research and claimed that he had created the virus (he would later also create the G-virus). As we all know Birkin died during the Raccoon City incident in 1998 (RE 2) along with his wife. Umbrellas other co-founder Edward Ashford had already died in the late 60s and his position went to his son Alexander (wo created T-veronica and used it to create the twins Alfred and Alexia in 1972). Alexander was infected with T-Veronica in 1982 and then killed in 1999 by Claire Redfield (Code Veronica). Alfred and Alexia were killed around the same time, eliminating the Ashord-line.
Thus Spencer had only Alex Wesker left. While he continued his Progenitor research at his own mansion, Alex worked on a new virus for him on a remote island (and eventually she would create the T-Phobos virus). However inspired by Albert, she eventually betrayed Spencer as well and disappeared along with all her research. With no other options left Spencer then reached out to Albert, who came to his mansion in 2006. Spencer revealed Alberts true origin and purpose to him but did not realize in his arrogance that this would not sway Albert to his side. Instead Albert killed Spencer and then formed the plan to achieve Spencers original plan and create a virus which would create superhumans and make him a god while killing all the weak. This eventually resulted in the creation of Uroboros in 2009 but he was stopped and killed by Chris and Sheva (RE 5).
Afterwards Alex (the last standing Umbrella member and Wesker) conducted an experiment with the T-Phobos virus on a remote island in 2010, infecting several members of Terrasave with it (among them Claire and Moira Burton) to see if there was one of them who could be immune to fear (as fear triggers the virus) and could serve as a new host body for Alex. Ultimately her experiment failed as her chosen vessel Natalia Korda proved too strong for her to take over and her remaining mutated form was killed by Barry and Claire in 2011 (Revelations 2)
However even after Spencers death and Umbrellas fall and the death of the Weskers and all Umbrella executives their legacy continued as their viruses continued to be used in Bioterrorism and in 2012 Derek C. Simmons (Head of the powerful organization known as "The Family") and his head scientist Carla Radames created the C-Virus, which was derived from Umbrellas Progenitor virus and caused the biggest viral outbreak in history in 2013 in China (RE 6). However both Simmons and Radames were killed and Albert Weskers son Jake Mueller provided his blood to create a vaccine against the C-Virus which effectively ended the threat.
It remains to be seen in future games wether or not Spencers legacy has finally been destroyed or if his work will continue to plague the world. But yes it all started with him and everything that ever happened in the entire series can be traced to his actions. Thus he might actually be the most important character in the entire RE mythology.
