My picks:

A is for Aristotle (Philosopher, scientist taught by Plato, found much of early philosophy/science)
B is for Buddha (Prince, priest, and founder of the religion/philosophy of Buddhism)
C is for Confucius (Philosopher, founder of Confucianism and much of Eastern philosophy)
D is for Darwin (Biologist, unleashed evolutionary enlightenment and creationist backlash alike)
E is for Einstein (Physicist, discovered Theory of Relativity, Laws of Space and Time, etc.)
F is for Freud (Psychologist, pioneered psychological and psycho-analytic theory)
G is for Galileo (Astronomer, physicist, invented the telescope, popularized Scientific Method)
H is for Homer (Author, epic poems formed the first foundations of Western Literature)
I is for Isabella I (Queen, financed Spain’s trips to the Americas, instituted Spanish Inquisition)
J is for Jesus (Religious activist, preacher, and founder/prophet of the religion of Christianity)
K is for Kepler (Astronomer, discoverer of laws of planetary motion
L is for Locke (Philosopher, theory of democracy formed basis for US/UK democratic systems)
M is for Muhammad (Military leader and founder/prophet of the religion of Islam)
N is for Newton (Physicist, discovered Laws of Gravity and Laws of Motion, etc.)
O is for Orwell (Author, arguably the most important author of the 20th Century)
P is for Plato (Philosopher, taught Aristotle, laid groundwork for most of Western philosophy)
Q is for Qin Shi Huangdi (Emperor, unified China for the first time, burned numerous texts)
R is for Rousseau (Philosopher, theory of democracy inspired French revolution and democracy)
S is for Shakespeare (Author, 37/38 plays, 154 sonnets, immensely influential in literary figure)
T is for Tzu (Philosopher, founder of the Taoist movement and ideology)
U is for Umar (Religious leader, took a lead in the early Islamic religion, engineered its growth)
V is for Victoria (Queen, ruled the British Empire for 60+ years, longest reign by a female leader)
W is for Washington (General, First President of, and “Father” of The United States of America)
X is for Xerxes (King, leader of Persian Empire I expansion and starting the Greco-Persian Wars)
Y is for Yat-sen (Activist, led of the Chinese Revolution, named by State as “Father” of nation)
Z is for Zoroaster (Prophet, founder of Zoroastrianism, influenced Abrahamic religions)

Top 10 Notables Left Off:
-Mozart (A victim of Muhammad’s getting the slot, “M” was one of the hardest to decide)
-Marx (Also ousted by Muhammad, as he, Engels, and Lenin all split credit for Communism)
-Moses (Also ousted by Muhammad; he, Mozart, Marx, and Muhammad were all close)
-Beethoven (A similar story to the “M’s,” B had a three-way race, and was hard to choose)
-Bach (See Beethoven; it’s a shame of the three, Bach/Beethoven/Mozart all missed out)
-Ghandi (He actually had the spot…and then I realized I’d left Galileo out…it was close, though)
-Luther (With enough religious figures already, I left Luther out in favor of Locke—and Reason)
-Hitler (Homer has a longer-standing influence…and I’d prefer as “positive” a thing as possible)
-Nietzsche (Shakespeare locked up his spot, but not Nietzsche…those pesky Laws of Motion…)
-Elizabeth I (Another great figure ousted by science…damn you, Theory of Relativity…)