Some of the many (semi)standard references are below (with no claims to completeness or representativeness, if that's a word -- just the first references that came to mind). My feeling is the subject is still very much in its infancy however, for example one would like to know the standard package of nonabelian Hodge theory results for singular curves (geometry of Higgs bundles and local systems, Hitchin fibration, its self-duality etc) and there are partial results but no complete picture as far as I know.
Caporaso, Lucia A compactification of the universal Picard variety over the moduli space of stable curves. J. Amer. Math. Soc. 7 (1994), no. 3, 589--660.
Pandharipande, Rahul A compactification over $\overline {M}_g$ of the universal moduli space of slope-semistable vector bundles. J. Amer. Math. Soc. 9 (1996), no. 2, 425--471.
Seshadri, C. S. Moduli spaces of torsion free sheaves on nodal curves and generalisations. I. Moduli spaces and vector bundles, 484--505, London Math. Soc. Lecture Note Ser., 359, Cambridge Univ. Press, Cambridge, 2009.
(and earlier papers of his)
arXiv:1001.3868 Title: Autoduality of compactified Jacobians for curves with plane singularities
Authors: D.Arinkin
--see this reference for refs to the vast literature by Altman-Kleiman and Esteves-Kleiman on compactified Jacobians
Kausz, Ivan A Gieseker type degeneration of moduli stacks of vector bundles on curves. Trans. Amer. Math. Soc. 357 (2005), no. 12, 4897--4955 (electronic).
Schmitt, Alexander H. W. Singular principal $G$-bundles on nodal curves. J. Eur. Math. Soc. (JEMS) 7 (2005), no. 2, 215--251.
(and earlier papers of his)
My favourite is Oda's Strong Factorization Conjecture:
Can a proper, birational map between smooth toric varieties be factored as a composition of a sequence of smooth toric blow-ups followed by a sequence smooth toric blow-downs?
Note that if you are allowed to intermingle the blow-ups and blow-downs (the weak version) it has been proved. In fact, it was proved for general varieties in characteristic 0 using the toric case:
Torification and Factorization of Birational Maps. Abramovich, Karu, Matsuki, Wlodarczyk.
A conjectural algorithm for computing toric strong factorizations can be found in the following arXiv article:
On Oda's Strong Factorization Conjecture. Da Silva, Karu.
Best Answer
A few of the more obvious ones:
* Resolution of singularities in characteristic p
*Hodge conjecture
* Standard conjectures on algebraic cycles (though these are not so urgent since Deligne proved the Weil conjectures).
*Proving finite generation of the canonical ring for general type used to be open though I think it was recently solved; I'm not sure about the details.
For vector bundles, a longstanding open problem is the classification of vector bundles over projective spaces.
(Added later) A very old major problem is that of finding which moduli spaces of curves are unirational. It is classical that the moduli space is unirational for genus at most 10, and I think this has more recently been pushed to genus about 13. Mumford and Harris showed that it is of general type for genus at least 24. As far as I know most of the remaining cases are still open.